{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:31:36Z","timestamp":1787567496472,"version":"build-2736575974"},"reference-count":95,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["5R01NS123644"],"award-info":[{"award-number":["5R01NS123644"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["3R01NS123644-02S1"],"award-info":[{"award-number":["3R01NS123644-02S1"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["1R56NS123644"],"award-info":[{"award-number":["1R56NS123644"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["10.58275\/aha.24post1196351.pc.gr.190837"],"award-info":[{"award-number":["10.58275\/aha.24post1196351.pc.gr.190837"],"id":[{"id":"10.58275\/aha.24post1196351.pc.gr.190837","id-type":"DOI","asserted-by":"publisher"}]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["3R01NS123644-02S2"],"award-info":[{"award-number":["3R01NS123644-02S2"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"award":["3R01NS123644-02S2"],"award-info":[{"award-number":["3R01NS123644-02S2"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Blood pressure variability (BPV) has emerged as a significant risk factor for cognitive decline and dementia, independent of alterations in average blood pressure (BP). However, the impact of large BP fluctuations on neurovascular function remains poorly understood. In this study, we developed a novel murine model of BPV in middle-aged mice using intermittent angiotensin II infusions. Radio telemetry confirmed that 24 hr BP averages in BPV mice remained comparable to controls, demonstrating BPV in the absence of hypertension. Chronic (20\u201325 days) BPV resulted in a blunted bradycardic response and cognitive deficits. Two-photon imaging revealed heightened pressure-evoked constrictions (myogenic response) in parenchymal arterioles of BPV mice. While sensory stimulus-evoked dilations (neurovascular coupling) were amplified at higher BP levels in control mice, this pressure-dependent effect was abolished in BPV mice. Our findings indicate that chronic BP fluctuations impair vascular function within the neurovascular complex and contribute to cognitive decline, emphasizing BPV as a critical factor in brain health.<\/jats:p>","DOI":"10.7554\/elife.104082","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T07:25:07Z","timestamp":1738567507000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.104082","source":"Crossref","is-referenced-by-count":3,"title":["Blood pressure variability compromises vascular function in middle-aged mice"],"prefix":"10.7554","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0428-6272","authenticated-orcid":true,"given":"Perenkita J","family":"Mendiola","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/012mef835","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Physiology, Medical College of Georgia, Augusta University","place":["Augusta, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8137-9432","authenticated-orcid":true,"given":"Philip","family":"O'Herron","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/012mef835","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Physiology, Medical College of Georgia, Augusta University","place":["Augusta, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Kun","family":"Xie","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/012mef835","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Physiology, Medical College of Georgia, Augusta University","place":["Augusta, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Michael W","family":"Brands","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/012mef835","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Physiology, Medical College of Georgia, Augusta University","place":["Augusta, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Weston","family":"Bush","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/012mef835","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Physiology, Medical College of Georgia, Augusta University","place":["Augusta, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Rachel E","family":"Patterson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/012mef835","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Physiology, Medical College of Georgia, Augusta University","place":["Augusta, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Valeria","family":"Di Stefano","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/012mef835","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Physiology, Medical College of Georgia, Augusta University","place":["Augusta, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7536-2039","authenticated-orcid":true,"given":"Jessica A","family":"Filosa","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/012mef835","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Physiology, Medical College of Georgia, Augusta University","place":["Augusta, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1113\/jphysiol.1978.sp012318","type":"journal-article","article-title":"The half-lives of angiotensin II, angiotensin II-amide, angiotensin III, Sar1-Ala8-angiotensin II and renin in the circulatory system of the rat","volume":"278","author":"Al-Merani","year":"1978","journal-title":"The Journal of Physiology"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/s10339-011-0430-z","type":"journal-article","article-title":"The novel object recognition memory: neurobiology, test procedure, and its modifications","volume":"13","author":"Antunes","year":"2012","journal-title":"Cognitive Processing"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1161\/HYPERTENSIONAHA.123.19939","type":"journal-article","article-title":"Basic mechanisms of brain injury and cognitive decline in hypertension","volume":"81","author":"Baggeroer","year":"2024","journal-title":"Hypertension"},{"key":"bib4","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2021.113630","type":"journal-article","article-title":"Effects of long-term social isolation on central, behavioural and metabolic parameters in middle-aged mice","volume":"417","author":"Benfato","year":"2022","journal-title":"Behavioural Brain Research"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1161\/HYPERTENSIONAHA.114.04568","type":"journal-article","article-title":"Systolic blood pressure variation and mean heart rate is associated with cognitive dysfunction in patients with high cardiovascular risk","volume":"65","author":"B\u00f6hm","year":"2015","journal-title":"Hypertension"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1161\/CIRCRESAHA.121.318061","type":"journal-article","article-title":"Arterial stiffness and cardiovascular risk in hypertension","volume":"128","author":"Boutouyrie","year":"2021","journal-title":"Circulation Research"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1161\/01.hyp.26.3.420","type":"journal-article","article-title":"Chronic infusion of angiotensin II resets baroreflex control of heart rate by an arterial pressure-independent mechanism","volume":"26","author":"Brooks","year":"1995","journal-title":"Hypertension"},{"key":"bib8","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-89245-w","type":"journal-article","article-title":"Differential effects of alkaloids on memory in rodents","volume":"11","author":"Callahan","year":"2021","journal-title":"Scientific Reports"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"4878","DOI":"10.1523\/JNEUROSCI.6262-11.2012","type":"journal-article","article-title":"Central cardiovascular circuits contribute to the neurovascular dysfunction in angiotensin II hypertension","volume":"32","author":"Capone","year":"2012","journal-title":"The Journal of Neuroscience"},{"key":"bib10","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13181","type":"journal-article","article-title":"Transient receptor potential vanilloid-4 channels are involved in diminished myogenic tone in brain parenchymal arterioles in response to chronic hypoperfusion in mice","volume":"225","author":"Chan","year":"2019","journal-title":"Acta Physiologica"},{"key":"bib11","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2013.00106","type":"journal-article","article-title":"Improved blood velocity measurements with a hybrid image filtering and iterative Radon transform algorithm","volume":"7","author":"Chhatbar","year":"2013","journal-title":"Frontiers in Neuroscience"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1152\/japplphysiol.00253.2014","type":"journal-article","article-title":"Increased pressure-induced tone in rat parenchymal arterioles vs. middle cerebral arteries: role of ion channels and calcium sensitivity","volume":"117","author":"Cipolla","year":"2014","journal-title":"Journal of Applied Physiology"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1152\/physrev.00022.2020","type":"journal-article","article-title":"Regulation of cerebral blood flow in humans: physiology and clinical implications of autoregulation","volume":"101","author":"Claassen","year":"2021","journal-title":"Physiological Reviews"},{"key":"bib14","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12196167","type":"journal-article","article-title":"Blood pressure variability as a risk factor for cardiovascular disease: which antihypertensive agents are more effective?","volume":"12","author":"de la Sierra","year":"2023","journal-title":"Journal of Clinical Medicine"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1161\/HYPERTENSIONAHA.117.09086","type":"journal-article","article-title":"Sustained reduction of blood pressure with baroreceptor activation therapy: results of the 6-year open follow-up","volume":"69","author":"de Leeuw","year":"2017","journal-title":"Hypertension"},{"key":"bib16","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000016347","type":"journal-article","article-title":"Blood pressure variability with different measurement methods: Reliability and predictors: A proof of concept cross sectional study in elderly hypertensive hospitalized patients","volume":"98","author":"Del Giorno","year":"2019","journal-title":"Medicine"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1002\/glia.23564","type":"journal-article","article-title":"Augmented astrocyte microdomain Ca 2+ dynamics and parenchymal arteriole tone in angiotensin II\u2010infused hypertensive mice","volume":"67","author":"Diaz","year":"2019","journal-title":"Glia"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1161\/HYPERTENSIONAHA.117.09598","type":"journal-article","article-title":"Endothelial mineralocorticoid receptor mediates parenchymal arteriole and posterior cerebral artery remodeling during angiotensin II-induced hypertension","volume":"70","author":"Diaz-Otero","year":"2017","journal-title":"Hypertension"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1212\/wnl.56.7.921","type":"journal-article","article-title":"Longitudinal study of blood pressure and white matter hyperintensities: the EVA MRI Cohort","volume":"56","author":"Dufouil","year":"2001","journal-title":"Neurology"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1111\/jch.13606","type":"journal-article","article-title":"Association between cerebral microbleeds and hypertension in the Swedish general population \u201cGood Aging in Sk\u00e5ne\u201d study","volume":"21","author":"Elmst\u00e5hl","year":"2019","journal-title":"Journal of Clinical Hypertension"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"2168","DOI":"10.1111\/jgs.12542","type":"journal-article","article-title":"Cognitive dysfunction and greater visit-to-visit systolic blood pressure variability","volume":"61","author":"Epstein","year":"2013","journal-title":"Journal of the American Geriatrics Society"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"1945","DOI":"10.1161\/HYPERTENSIONAHA.120.16209","type":"journal-article","article-title":"Long-term blood pressure variability and risk of cardiovascular disease events among community-dwelling elderly","volume":"76","author":"Ernst","year":"2020","journal-title":"Hypertension"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"H738","DOI":"10.1152\/ajpheart.1987.252.4.H738","type":"journal-article","article-title":"Segmental vascular responses to acute hypertension in cerebrum and brain stem","volume":"252","author":"Faraci","year":"1987","journal-title":"The American Journal of Physiology"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1161\/01.res.66.1.8","type":"journal-article","article-title":"Regulation of large cerebral arteries and cerebral microvascular pressure","volume":"66","author":"Faraci","year":"1990","journal-title":"Circulation Research"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"4674","DOI":"10.1172\/JCI86950","type":"journal-article","article-title":"Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension","volume":"126","author":"Faraco","year":"2016","journal-title":"The Journal of Clinical Investigation"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1136\/jnnp.1.3.187","type":"journal-article","article-title":"The relationship between the blood pressure and the tonic regulation of the pial arteries","volume":"1","author":"Fog","year":"1938","journal-title":"Journal of Neurology and Psychiatry"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"e117","DOI":"10.1161\/01.CIR.0000070983.15903.A2","type":"journal-article","article-title":"Cardiology patient page: Beta-adrenergic blockers","volume":"107","author":"Frishman","year":"2003","journal-title":"Circulation"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"F772","DOI":"10.1152\/ajprenal.00019.2008","type":"journal-article","article-title":"Intrarenal angiotensin II and angiotensinogen augmentation in chronic angiotensin II-infused mice","volume":"295","author":"Gonzalez-Villalobos","year":"2008","journal-title":"American Journal of Physiology. Renal Physiology"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/sj.cr.7290083","type":"journal-article","article-title":"The angiotensin II type 1 receptor and receptor-associated proteins","volume":"11","author":"Guo","year":"2001","journal-title":"Cell Research"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1161\/HYPERTENSIONAHA.107.090308","type":"journal-article","article-title":"Baroreflex sensitivity inversely correlates with ambulatory blood pressure in healthy normotensive humans","volume":"50","author":"Hesse","year":"2007","journal-title":"Hypertension"},{"key":"bib31","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2023.1186073","type":"journal-article","article-title":"Analysis of the influences of social isolation on cognition and the therapeutic potential of deep brain stimulation in a mouse model","volume":"14","author":"Hu","year":"2023","journal-title":"Frontiers in Psychiatry"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/s0167-0115(00)00137-3","type":"journal-article","article-title":"Mechanisms and functions of AT(1) angiotensin receptor internalization","volume":"91","author":"Hunyady","year":"2000","journal-title":"Regulatory Peptides"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1016\/j.cmet.2008.03.010","type":"journal-article","article-title":"Hypertension and cerebrovascular dysfunction","volume":"7","author":"Iadecola","year":"2008","journal-title":"Cell Metabolism"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"e67","DOI":"10.1161\/HYP.0000000000000053","type":"journal-article","article-title":"Impact of hypertension on cognitive function: a scientific statement from the american heart association","volume":"68","author":"Iadecola","year":"2016","journal-title":"Hypertension"},{"key":"bib35","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.07.030","type":"journal-article","article-title":"The neurovascular unit coming of age: a journey through neurovascular coupling in health and disease","volume":"96","author":"Iadecola","year":"2017","journal-title":"Neuron"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1038\/jcbfm.2015.31","type":"journal-article","article-title":"Enhanced parenchymal arteriole tone and astrocyte signaling protect neurovascular coupling mediated parenchymal arteriole vasodilation in the spontaneously hypertensive rat","volume":"35","author":"Iddings","year":"2015","journal-title":"Journal of Cerebral Blood Flow and Metabolism"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1097\/01.hjh.0000222757.54111.06","type":"journal-article","article-title":"Middle cerebral artery structure and distensibility during developing and established phases of hypertension in the spontaneously hypertensive rat","volume":"24","author":"Izzard","year":"2006","journal-title":"Journal of Hypertension"},{"key":"bib38","first-page":"8","type":"journal-article","article-title":"A retrospective study of idiopathic ulcerative dermatitis in mice with a C57BL\/6 background","volume":"45","author":"Kastenmayer","year":"2006","journal-title":"Journal of the American Association for Laboratory Animal Science"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1007\/s11357-020-00305-x","type":"journal-article","article-title":"Decreased parenchymal arteriolar tone uncouples vessel-to-neuronal communication in a mouse model of vascular cognitive impairment","volume":"43","author":"Kim","year":"2021","journal-title":"GeroScience"},{"key":"bib40","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.121.022943","type":"journal-article","article-title":"Differential hemodynamic response of pial arterioles contributes to a quadriphasic cerebral autoregulation physiology","volume":"11","author":"Klein","year":"2022","journal-title":"Journal of the American Heart Association"},{"key":"bib41","doi-asserted-by":"publisher","DOI":"10.1172\/JCI149029","type":"journal-article","article-title":"Differential restoration of functional hyperemia by antihypertensive drug classes in hypertension-related cerebral small vessel disease","volume":"131","author":"Koide","year":"2021","journal-title":"The Journal of Clinical Investigation"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"H371","DOI":"10.1152\/ajpheart.1978.234.4.H371","type":"journal-article","article-title":"Responses of cerebral arteries and arterioles to acute hypotension and hypertension","volume":"234","author":"Kontos","year":"1978","journal-title":"The American Journal of Physiology"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/978-1-4939-8994-2_10","type":"journal-article","article-title":"The Y-maze for assessment of spatial working and reference memory in mice","volume":"1916","author":"Kraeuter","year":"2019","journal-title":"Methods in Molecular Biology"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.bbr.2016.09.005","type":"journal-article","article-title":"Differential effects of social isolation in adolescent and adult mice on behavior and cortical gene expression","volume":"316","author":"Lander","year":"2017","journal-title":"Behavioural Brain Research"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1152\/physrev.1959.39.2.183","type":"journal-article","article-title":"Cerebral blood flow and oxygen consumption in man","volume":"39","author":"Lassen","year":"1959","journal-title":"Physiological Reviews"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"9836","DOI":"10.1523\/JNEUROSCI.4943-10.2011","type":"journal-article","article-title":"Pyramidal neurons are \u201cneurogenic hubs\u201d in the neurovascular coupling response to whisker stimulation","volume":"31","author":"Lecrux","year":"2011","journal-title":"The Journal of Neuroscience"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1038\/hr.2014.33","type":"journal-article","article-title":"Antihypertensive drug classes have different effects on short-term blood pressure variability in essential hypertension","volume":"37","author":"Levi-Marpillat","year":"2014","journal-title":"Hypertension Research"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"119","DOI":"10.21037\/qims-21-28","type":"journal-article","article-title":"White matter changes, duration of hypertension, and age are associated with cerebral microbleeds in patients with different stages of hypertension","volume":"12","author":"Liang","year":"2022","journal-title":"Quantitative Imaging in Medicine and Surgery"},{"key":"bib49","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52969-0","type":"journal-article","article-title":"Endothelial Piezo1 channel mediates mechano-feedback control of brain blood flow","volume":"15","author":"Lim","year":"2024","journal-title":"Nature Communications"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"2694","DOI":"10.1111\/ejn.14565","type":"journal-article","article-title":"Single housing-induced effects on cognitive impairment and depression-like behavior in male and female mice involve neuroplasticity-related signaling","volume":"52","author":"Liu","year":"2020","journal-title":"The European Journal of Neuroscience"},{"key":"bib51","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4533","type":"journal-article","article-title":"Capillary K(+)-sensing initiates retrograde hyperpolarization to increase local cerebral blood flow","volume":"20","author":"Longden","year":"2017","journal-title":"Nature Neuroscience"},{"key":"bib52","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.29.6.1329","type":"journal-article","article-title":"Effects of age on Ca2+ currents in small mesenteric artery myocytes from Wistar-Kyoto and spontaneously hypertensive rats","volume":"29","author":"Lozinskaya","year":"1997","journal-title":"Hypertension"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"H1085","DOI":"10.1152\/ajpheart.1996.270.3.H1085","type":"journal-article","article-title":"Regional cerebral blood flow response to vibrissal stimulation in mice lacking type I NOS gene expression","volume":"270","author":"Ma","year":"1996","journal-title":"The American Journal of Physiology"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"2387","DOI":"10.1016\/j.jacc.2020.03.043","type":"journal-article","article-title":"Blood pressure variation and subclinical brain disease","volume":"75","author":"Ma","year":"2020","journal-title":"Journal of the American College of Cardiology"},{"key":"bib55","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2024.105678","type":"journal-article","article-title":"Age-related impact of social isolation in mice: Young vs middle-aged","volume":"174","author":"Magalh\u00e3es","year":"2024","journal-title":"Neurochemistry International"},{"key":"bib56","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0248362","type":"journal-article","article-title":"Visit-to-visit blood pressure variability is common in primary care patients: Retrospective cohort study of 221,803 adults","volume":"16","author":"McAlister","year":"2021","journal-title":"PLOS ONE"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"2447","DOI":"10.1212\/WNL.0000000000004741","type":"journal-article","article-title":"Blood pressure from mid- to late life and risk of incident dementia","volume":"89","author":"McGrath","year":"2017","journal-title":"Neurology"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"1556","DOI":"10.1097\/HJH.0b013e3283552735","type":"journal-article","article-title":"Visit-to-visit blood pressure variations: new independent determinants for cognitive function in the elderly at high risk of cardiovascular disease","volume":"30","author":"Nagai","year":"2012","journal-title":"Journal of Hypertension"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1161\/HYPERTENSIONAHA.120.14972","type":"journal-article","article-title":"Increased susceptibility of mice lacking renin-b to angiotensin II-induced organ damage","volume":"76","author":"Nakagawa","year":"2020","journal-title":"Hypertension"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1161\/CIRCRESAHA.109.213363","type":"journal-article","article-title":"Increased coupled gating of L-type Ca2+ channels during hypertension and Timothy syndrome","volume":"106","author":"Navedo","year":"2010","journal-title":"Circulation Research"},{"key":"bib61","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12423","type":"journal-article","article-title":"Regulation of voltage\u2010gated potassium channels in vascular smooth muscle during hypertension and metabolic disorders","volume":"25","author":"Nieves\u2010Cintr\u00f3n","year":"2018","journal-title":"Microcirculation"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1007\/s12576-019-00704-6","type":"journal-article","article-title":"Cerebral blood flow regulation and cognitive function: a role of arterial baroreflex function","volume":"69","author":"Ogoh","year":"2019","journal-title":"The Journal of Physiological Sciences"},{"key":"bib63","doi-asserted-by":"publisher","DOI":"10.1038\/nature17965","type":"journal-article","article-title":"Neural correlates of single-vessel haemodynamic responses in vivo","volume":"534","author":"O\u2019Herron","year":"2016","journal-title":"Nature"},{"key":"bib64","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.72802","type":"journal-article","article-title":"3D optogenetic control of arteriole diameter in vivo","volume":"11","author":"O\u2019Herron","year":"2022","journal-title":"eLife"},{"key":"bib65","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1093\/ajh\/hpab125","type":"journal-article","article-title":"Does blood pressure variability affect hypertension development in prehypertensive patients?","volume":"35","author":"\u00d6zkan","year":"2022","journal-title":"American Journal of Hypertension"},{"key":"bib66","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2020.111337","type":"journal-article","article-title":"Effects of age and social isolation on murine hippocampal biochemistry and behavior","volume":"191","author":"Panossian","year":"2020","journal-title":"Mechanisms of Ageing and Development"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1111\/jch.13304","type":"journal-article","article-title":"Blood pressure variability: clinical relevance and application","volume":"20","author":"Parati","year":"2018","journal-title":"The Journal of Clinical Hypertension"},{"key":"bib68","doi-asserted-by":"publisher","first-page":"e97","DOI":"10.1161\/01.RES.0000131495.93500.3c","type":"journal-article","article-title":"High blood pressure upregulates arterial L-type Ca2+ channels: is membrane depolarization the signal","volume":"94","author":"Pesic","year":"2004","journal-title":"Circulation Research"},{"key":"bib69","doi-asserted-by":"publisher","first-page":"H127","DOI":"10.1152\/ajpheart.00168.2015","type":"journal-article","article-title":"Regulation of myogenic tone and structure of parenchymal arterioles by hypertension and the mineralocorticoid receptor","volume":"309","author":"Pires","year":"2015","journal-title":"American Journal of Physiology. Heart and Circulatory Physiology"},{"key":"bib70","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1161\/01.hyp.0000025877.23309.36","type":"journal-article","article-title":"Upregulation of L-type Ca2+ channels in mesenteric and skeletal arteries of SHR","volume":"40","author":"Pratt","year":"2002","journal-title":"Hypertension"},{"key":"bib71","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1097\/HJH.0000000000001153","type":"journal-article","article-title":"Morning pressor surge, blood pressure variability, and arterial stiffness in essential hypertension","volume":"35","author":"Pucci","year":"2017","journal-title":"Journal of Hypertension"},{"key":"bib72","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1159\/000508760","type":"journal-article","article-title":"Hypertension-Related Cerebral Microbleeds","volume":"12","author":"Reddy","year":"2020","journal-title":"Case Reports in Neurology"},{"key":"bib73","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-024-05996-y","type":"journal-article","article-title":"Modulatory effects of noradrenergic and serotonergic signaling pathway on neurovascular coupling","volume":"7","author":"Renden","year":"2024","journal-title":"Communications Biology"},{"key":"bib74","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1038\/ajh.2011.20","type":"journal-article","article-title":"Effects of spironolactone on cerebral vessel structure in rats with sustained hypertension","volume":"24","author":"Rigsby","year":"2011","journal-title":"American Journal of Hypertension"},{"key":"bib75","doi-asserted-by":"publisher","first-page":"1912","DOI":"10.1056\/NEJM199312233292602","type":"journal-article","article-title":"The natural history of borderline isolated systolic hypertension","volume":"329","author":"Sagie","year":"1993","journal-title":"The New England Journal of Medicine"},{"key":"bib76","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1161\/HYPERTENSIONAHA.122.18085","type":"journal-article","article-title":"Hypertension, neurovascular dysfunction, and cognitive impairment","volume":"80","author":"Santisteban","year":"2023","journal-title":"Hypertension"},{"key":"bib77","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00904-7","type":"journal-article","article-title":"Revisiting the neurovascular unit","volume":"24","author":"Schaeffer","year":"2021","journal-title":"Nature Neuroscience"},{"key":"bib78","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-022-00690-0","type":"journal-article","article-title":"Blood pressure and its variability: classic and novel measurement techniques","volume":"19","author":"Schutte","year":"2022","journal-title":"Nature Reviews Cardiology"},{"key":"bib79","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1093\/ajh\/hpac128","type":"journal-article","article-title":"Blood pressure variability and cognitive decline: a post Hoc analysis of the SPRINT MIND trial","volume":"36","author":"Sible","year":"2023","journal-title":"American Journal of Hypertension"},{"key":"bib80","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.1161\/01.RES.82.12.1330","type":"journal-article","article-title":"Increase in functional Ca2+ channels in cerebral smooth muscle with renal hypertension","volume":"82","author":"Simard","year":"1998","journal-title":"Circulation Research"},{"key":"bib81","doi-asserted-by":"publisher","DOI":"10.1186\/s42826-024-00221-7","type":"journal-article","article-title":"Effects of single housing on behavior, corticosterone level and body weight in male and female mice","volume":"40","author":"Smolensky","year":"2024","journal-title":"Laboratory Animal Research"},{"key":"bib82","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.vph.2005.10.005","type":"journal-article","article-title":"Vascular calcium channels and high blood pressure: Pathophysiology and therapeutic implications","volume":"44","author":"Sonkusare","year":"2006","journal-title":"Vascular Pharmacology"},{"key":"bib83","doi-asserted-by":"publisher","first-page":"255","DOI":"10.30802\/AALAS-CM-23-000033","type":"journal-article","article-title":"Seasonal variation of laboratory animals as a consideration for research reproducibility","volume":"73","author":"Suckow","year":"2023","journal-title":"Comparative Medicine"},{"key":"bib84","doi-asserted-by":"publisher","first-page":"1871","DOI":"10.1038\/jcbfm.2015.162","type":"journal-article","article-title":"Pharmacologically-induced neurovascular uncoupling is associated with cognitive impairment in mice","volume":"35","author":"Tarantini","year":"2015","journal-title":"Journal of Cerebral Blood Flow and Metabolism"},{"key":"bib85","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.neuroimage.2015.01.041","type":"journal-article","article-title":"Central artery stiffness, baroreflex sensitivity, and brain white matter neuronal fiber integrity in older adults","volume":"110","author":"Tarumi","year":"2015","journal-title":"NeuroImage"},{"key":"bib86","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1007\/s00421-018-4036-3","type":"journal-article","article-title":"Ageing affects the balance between central and peripheral mechanisms of cerebrovascular regulation with increasing influence of systolic blood pressure levels","volume":"119","author":"Teixeira","year":"2019","journal-title":"European Journal of Applied Physiology"},{"key":"bib87","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1161\/01.STR.29.6.1194","type":"journal-article","article-title":"High levels of myogenic tone antagonize the dilator response to flow of small rabbit cerebral arteries","volume":"29","author":"Thorin-Trescases","year":"1998","journal-title":"Stroke"},{"key":"bib88","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1016\/j.neuron.2018.09.045","type":"journal-article","article-title":"Astrocytes integrate behavioral state and vascular signals during functional hyperemia","volume":"100","author":"Tran","year":"2018","journal-title":"Neuron"},{"key":"bib89","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1161\/01.HYP.0000145857.98904.20","type":"journal-article","article-title":"The association between blood pressure, hypertension, and cerebral white matter lesions: cardiovascular determinants of dementia study","volume":"44","author":"van Dijk","year":"2004","journal-title":"Hypertension"},{"key":"bib90","doi-asserted-by":"publisher","first-page":"2422","DOI":"10.1097\/HJH.0000000000000739","type":"journal-article","article-title":"Blood pressure variability predicts cardiovascular events independently of traditional cardiovascular risk factors and target organ damage: a LIFE substudy","volume":"33","author":"Vishram","year":"2015","journal-title":"Journal of Hypertension"},{"key":"bib91","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1161\/HYPERTENSIONAHA.107.089391","type":"journal-article","article-title":"Isolated systolic hypertension is characterized by increased aortic stiffness and endothelial dysfunction","volume":"50","author":"Wallace","year":"2007","journal-title":"Hypertension"},{"key":"bib92","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/hr.2011.203","type":"journal-article","article-title":"Blood pressure variability in relation to autonomic nervous system dysregulation: the X-CELLENT study","volume":"35","author":"Zhang","year":"2012","journal-title":"Hypertension Research"},{"key":"bib93","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1161\/HYPERTENSIONAHA.122.19269","type":"journal-article","article-title":"Day to day blood pressure variability associated with cerebral arterial dilation and white matter hyperintensity","volume":"79","author":"Zhang","year":"2022","journal-title":"Hypertension"},{"key":"bib94","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1111\/jch.14831","type":"journal-article","article-title":"Relationship between morning blood pressure variability and cerebral microbleed burden in patients with hypertension","volume":"26","author":"Zhang","year":"2024","journal-title":"Journal of Clinical Hypertension"},{"key":"bib95","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1161\/01.RES.0000135483.12297.e4","type":"journal-article","article-title":"Hypertension caused by angiotensin II infusion involves increased superoxide production in the central nervous system","volume":"95","author":"Zimmerman","year":"2004","journal-title":"Circulation Research"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/104082\/elife-104082-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/104082\/elife-104082-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/104082","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:19:11Z","timestamp":1787563151000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/104082"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,22]]},"references-count":95,"alternative-id":["10.7554\/eLife.104082"],"URL":"https:\/\/doi.org\/10.7554\/elife.104082","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.10.21.619509","asserted-by":"subject"}],"is-same-as":[{"id-type":"doi","id":"10.7554\/eLife.104082.3","asserted-by":"subject"}],"is-version-of":[{"id-type":"doi","id":"10.7554\/eLife.104082.1","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.104082.2","asserted-by":"subject"}],"is-financed-by":[{"id-type":"doi","id":"10.58275\/aha.24post1196351.pc.gr.190837","asserted-by":"subject"},{"id-type":"doi","id":"10.58275\/AHA.24POST1196351.pc.gr.190837","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,22]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"RP104082"}}