{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:00:39Z","timestamp":1787029239876,"version":"build-2736575974"},"reference-count":50,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PSC CUNY Cycle 54 Award","award":["66608-00 54"],"award-info":[{"award-number":["66608-00 54"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathophysiology"],"abstract":"<jats:p>High systolic blood pressure and increased blood pressure variability after the onset of ischemic stroke are associated with poor clinical outcomes. One of the key determinants of blood pressure is arteriolar size, determined by vascular smooth muscle tone and vasodilatory and vasoconstrictor substances that are released by the endothelium. The aim of this study is to outline alterations in vasomotor function in isolated peripheral arteries following ischemic stroke. The reactivity of thoracic aortic segments from male C57BL\/6 mice to dilators and constrictors was quantified using wire myography. Acetylcholine-induced endothelium-dependent vasodilation was impaired after ischemic stroke (LogIC50 Sham = \u22127.499, LogIC50 Stroke = \u22127.350, p = 0.0132, n = 19, 31 respectively). The vasodilatory responses to SNP were identical in the isolated aortas in the sham and stroke groups. Phenylephrine-induced vasoconstriction was impaired in the aortas isolated from the stroke animals in comparison to their sham treatment counterparts (Sham LogEC50= \u22126.652 vs. Stroke LogEC50 = \u22126.475, p &lt; 0.001). Our study demonstrates that 24 h post-ischemic stroke, peripheral vascular responses are impaired in remote arteries. The aortas from the stroke animals exhibited reduced vasoconstrictor and endothelium-dependent vasodilator responses, while the endothelium-independent vasodilatory responses were preserved. Since both the vasodilatory and vasoconstrictor responses of peripheral arteries are impaired following ischemic stroke, our findings might explain increased blood pressure variability following ischemic stroke.<\/jats:p>","DOI":"10.3390\/pathophysiology31030036","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T05:30:02Z","timestamp":1725514202000},"page":"488-501","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Impaired Peripheral Vascular Function Following Ischemic Stroke in Mice: Potential Insights into Blood Pressure Variations in the Post-Stroke Patient"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4892-0984","authenticated-orcid":false,"given":"Gokhan","family":"Yilmaz","sequence":"first","affiliation":[{"name":"Molecular Cellular and Biomedical Sciences, CUNY School of Medicine, New York, NY 10031, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6975-3711","authenticated-orcid":false,"given":"Jonathan Steven","family":"Alexander","sequence":"additional","affiliation":[{"name":"Molecular & Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e254","DOI":"10.1161\/CIR.0000000000000950","article-title":"Heart Disease and Stroke Statistics-2021 Update: A Report from the American Heart Association","volume":"143","author":"Virani","year":"2021","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e153","DOI":"10.1161\/CIR.0000000000001052","article-title":"Heart Disease and Stroke Statistics-2022 Update: A Report from the American Heart Association","volume":"145","author":"Tsao","year":"2022","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1056\/NEJMoa1414792","article-title":"Endovascular therapy for ischemic stroke with perfusion-imaging selection","volume":"372","author":"Campbell","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1002\/ana.20741","article-title":"1,026 experimental treatments in acute stroke","volume":"59","author":"Macleod","year":"2006","journal-title":"Ann. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1177\/0271678X18800589","article-title":"The importance of comorbidities in ischemic stroke: Impact of hypertension on the cerebral circulation","volume":"38","author":"Cipolla","year":"2018","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1161\/STROKEAHA.118.020376","article-title":"Multimorbidity in Stroke","volume":"50","author":"Gallacher","year":"2019","journal-title":"Stroke"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1161\/STROKEAHA.115.010075","article-title":"Prognostic Significance of Short-Term Blood Pressure Variability in Acute Stroke: Systematic Review","volume":"46","author":"Manning","year":"2015","journal-title":"Stroke"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1212\/WNL.0000000000200856","article-title":"Blood Pressure Variability After Cerebrovascular Events: A Possible New Therapeutic Target: A Narrative Review","volume":"99","author":"Hawkes","year":"2022","journal-title":"Neurology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"941783","DOI":"10.1155\/2013\/941783","article-title":"Elevated blood pressure in the acute phase of stroke and the role of Angiotensin receptor blockers","volume":"2013","author":"Lattanzi","year":"2013","journal-title":"Int. J. Hypertens."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/svn-2016-000057","article-title":"Determinants of the impact of blood pressure variability on neurological outcome after acute ischaemic stroke","volume":"2","author":"Bennett","year":"2017","journal-title":"Stroke Vasc. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1097\/HJH.0000000000000675","article-title":"Blood pressure variability and the development of early neurological deterioration following acute ischemic stroke","volume":"33","author":"Chung","year":"2015","journal-title":"J. Hypertens."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2048004019856496","DOI":"10.1177\/2048004019856496","article-title":"Increased blood pressure variability after acute ischemic stroke increases the risk of death: A secondary analysis of the Virtual International Stroke Trial Archive","volume":"8","author":"Stoddard","year":"2019","journal-title":"JRSM Cardiovasc. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1161\/STROKEAHA.117.019312","article-title":"Autonomic Dysfunction Predicts Clinical Outcomes After Acute Ischemic Stroke","volume":"49","author":"Xiong","year":"2018","journal-title":"Stroke"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.1172\/JCI135530","article-title":"Immune responses to stroke: Mechanisms, modulation, and therapeutic potential","volume":"130","author":"Iadecola","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1161\/01.STR.32.2.413","article-title":"Stroke severity determines body temperature in acute stroke","volume":"32","author":"Boysen","year":"2001","journal-title":"Stroke"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1111\/j.1365-2796.2006.01635.x","article-title":"Endothelium-dependent vasodilatation in forearm is impaired in stroke patients","volume":"259","author":"Stenborg","year":"2006","journal-title":"J. Intern. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1212\/01.wnl.0000237526.32692.67","article-title":"Changes of brachial flow-mediated vasodilation in different ischemic stroke subtypes","volume":"67","author":"Chen","year":"2006","journal-title":"Neurology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1080\/00207454.2016.1198344","article-title":"The relationship of pro-inflammatory markers to vascular endothelial function after acute stroke","volume":"127","author":"Billinger","year":"2017","journal-title":"Int. J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/2040-7378-2-11","article-title":"Induction of neuro-protective\/regenerative genes in stem cells infiltrating post-ischemic brain tissue","volume":"2","author":"Yilmaz","year":"2010","journal-title":"Exp. Transl. Stroke Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/978-1-4939-2929-0_18","article-title":"Wire Myography to Study Vascular Tone and Vascular Structure of Isolated Mouse Arteries","volume":"1339","author":"Ferrer","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"H77","DOI":"10.1152\/ajpheart.01021.2020","article-title":"Guidelines for the measurement of vascular function and structure in isolated arteries and veins","volume":"321","author":"Wenceslau","year":"2021","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.apha.2016.05.001","article-title":"The Endothelium-Dependent Nitric Oxide-cGMP Pathway","volume":"77","author":"Monica","year":"2016","journal-title":"Adv. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1038\/sj.bjp.0701461","article-title":"Characterization of \u03b11-adrenoceptor subtypes mediating contractions to phenylephrine in rat thoracic aorta, mesenteric artery and pulmonary artery","volume":"122","author":"Hussain","year":"1997","journal-title":"Br. J. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1161\/CIRCRESAHA.116.306531","article-title":"Thirty Years of Saying NO: Sources, Fate, Actions, and Misfortunes of the Endothelium-Derived Vasodilator Mediator","volume":"119","author":"Vanhoutte","year":"2016","journal-title":"Circ. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1056\/NEJM199007053230105","article-title":"Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension","volume":"323","author":"Panza","year":"1990","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1161\/01.CIR.91.6.1732","article-title":"Impaired endothelium-dependent vasodilation in patients with essential hypertension. Evidence that nitric oxide abnormality is not localized to a single signal transduction pathway","volume":"91","author":"Panza","year":"1995","journal-title":"Circulation"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1097\/00004872-200304000-00003","article-title":"International Society of Hypertension (ISH): Statement on the management of blood pressure in acute stroke","volume":"21","author":"Bath","year":"2003","journal-title":"J. Hypertens."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/j.1600-0404.2006.00578.x","article-title":"Flow-mediated dilatation and intima-media thickness in patients with lacunar infarctions","volume":"113","author":"Sabovic","year":"2006","journal-title":"Acta Neurol. Scand"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1161\/01.STR.0000014509.11540.66","article-title":"Blood pressure and clinical outcomes in the International Stroke Trial","volume":"33","author":"Bath","year":"2002","journal-title":"Stroke"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"105211","DOI":"10.1016\/j.jstrokecerebrovasdis.2020.105211","article-title":"Blood Pressure and Hospital Discharge Outcomes in Acute Ischemic Stroke Patients Undergoing Reperfusion Therapy","volume":"29","author":"Jillella","year":"2020","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2849","DOI":"10.1161\/STROKEAHA.109.549618","article-title":"The spectrum of systemic immune alterations after murine focal ischemia: Immunodepression versus immunomodulation","volume":"40","author":"Liesz","year":"2009","journal-title":"Stroke"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1161\/CIRCULATIONAHA.105.593046","article-title":"Role of T lymphocytes and interferon-gamma in ischemic stroke","volume":"113","author":"Yilmaz","year":"2006","journal-title":"Circulation"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Lucaciu, A., Kuhn, H., Trautmann, S., Ferreiros, N., Steinmetz, H., Pfeilschifter, J., Brunkhorst, R., Pfeilschifter, W., Subburayalu, J., and Vutukuri, R. (2020). A Sphingosine 1-Phosphate Gradient Is Linked to the Cerebral Recruitment of T Helper and Regulatory T Helper Cells during Acute Ischemic Stroke. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176242"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2560","DOI":"10.1161\/STROKEAHA.107.513150","article-title":"Blood cell-derived RANTES mediates cerebral microvascular dysfunction, inflammation, and tissue injury after focal ischemia-reperfusion","volume":"39","author":"Terao","year":"2008","journal-title":"Stroke"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1007\/s12975-016-0449-7","article-title":"Effects of Acute Stroke Serum on Non-Ischemic Cerebral and Mesenteric Vascular Function","volume":"7","author":"Canavero","year":"2016","journal-title":"Transl. Stroke Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1007\/s12975-022-01117-1","article-title":"Serum from Stroke Patients with High-Grade Carotid Stenosis Promotes Cyclooxygenase-Dependent Endothelial Dysfunction in Non-ischemic Mice Carotid Arteries","volume":"15","author":"Puig","year":"2024","journal-title":"Transl. Stroke Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1113\/EP086510","article-title":"Circulating leucocytes perpetuate stroke-induced aortic dysfunction","volume":"102","author":"Asano","year":"2017","journal-title":"Exp. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1093\/ajh\/hpv034","article-title":"Blood Neutrophil to Lymphocyte Ratio as a Predictor of Hypertension","volume":"28","author":"Liu","year":"2015","journal-title":"Am. J. Hypertens."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1179\/174313208X341085","article-title":"Cell adhesion molecules and ischemic stroke","volume":"30","author":"Yilmaz","year":"2008","journal-title":"Neurol. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1097\/FJC.0b013e318281fa2d","article-title":"Contribution of alpha-adrenoceptor stimulation by phenylephrine to basal nitric oxide production in the isolated mouse aorta","volume":"61","author":"Schrijvers","year":"2013","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3687","DOI":"10.1111\/bph.13157","article-title":"alpha1 -Adrenoceptor activation of PKC-epsilon causes heterologous desensitization of thromboxane receptors in the aorta of spontaneously hypertensive rats","volume":"172","author":"Zhao","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/S0008-6363(95)00101-8","article-title":"Effects of inflammatory cytokines on vascular tone","volume":"30","author":"Ohkawa","year":"1995","journal-title":"Cardiovasc. Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Zhu, Y., Wu, M., Wang, H., Zheng, Y., Zhang, S., Wang, X., Wang, S., and Fang, Z. (2022). Daily blood pressure variability in relation to neurological functional outcomes after acute ischemic stroke. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.958166"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1177\/23969873221078136","article-title":"Pressor therapy in acute ischaemic stroke: An updated systematic review","volume":"7","author":"Stromsnes","year":"2022","journal-title":"Eur. Stroke J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e1955","DOI":"10.1212\/WNL.0000000000008520","article-title":"Therapeutic-induced hypertension in patients with noncardioembolic acute stroke","volume":"93","author":"Bang","year":"2019","journal-title":"Neurology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"187","DOI":"10.3988\/jcn.2007.3.4.187","article-title":"Induced hypertensive therapy in an acute ischemic stroke patient with early neurological deterioration","volume":"3","author":"Kim","year":"2007","journal-title":"J. Clin. Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"S157","DOI":"10.1016\/0006-2952(91)90406-U","article-title":"Nitric oxide generation from nitroprusside by vascular tissue. Evidence that reduction of the nitroprusside anion and cyanide loss are required","volume":"42","author":"Bates","year":"1991","journal-title":"Biochem. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1161\/01.CIR.100.23.2336","article-title":"Subtype specific regulation of human vascular alpha(1)-adrenergic receptors by vessel bed and age","volume":"100","author":"Rudner","year":"1999","journal-title":"Circulation"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1007\/s12975-017-0520-z","article-title":"MiR-126 Affects Brain-Heart Interaction after Cerebral Ischemic Stroke","volume":"8","author":"Chen","year":"2017","journal-title":"Transl. Stroke Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1001\/jamaneurol.2019.4838","article-title":"Blood Pressure Thresholds and Neurologic Outcomes after Endovascular Therapy for Acute Ischemic Stroke: An Analysis of Individual Patient Data from 3 Randomized Clinical Trials","volume":"77","author":"Rasmussen","year":"2020","journal-title":"JAMA Neurol."}],"container-title":["Pathophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1873-149X\/31\/3\/36\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:49:05Z","timestamp":1760111345000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1873-149X\/31\/3\/36"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,5]]},"references-count":50,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["pathophysiology31030036"],"URL":"https:\/\/doi.org\/10.3390\/pathophysiology31030036","relation":{},"ISSN":["1873-149X"],"issn-type":[{"value":"1873-149X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,5]]}}}