{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T02:59:21Z","timestamp":1782442761473,"version":"3.54.5"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T00:00:00Z","timestamp":1622678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Excessive sympathetic activation plays crucial roles in the pathogenesis of hypertension. Chemical stimulation of renal afferents increases the sympathetic activity and blood pressure in normal rats. This study investigated the excitatory renal reflex (ERR) in the development of hypertension in the spontaneously hypertensive rat (SHR). Experiments were performed in the Wistar-Kyoto rat (WKY) and SHR aged at 4, 12, and 24 weeks under anesthesia. Renal infusion of capsaicin was used to stimulate renal afferents, and thus, to induce ERR. The ERR was evaluated by the changes in the contralateral renal sympathetic nerve activity and mean arterial pressure. At the age of 4 weeks, the early stage with a slight or moderate hypertension, the ERR was more enhanced in SHR compared with WKY. The pressor response was greater than the sympathetic activation response in the SHR. At the age of 12 weeks, the development stage with severe hypertension, there was no significant difference in the ERR between the WKY and SHR. At the age of 24 weeks, the later stage of hypertension with long-term several hypertensions, the ERR was more attenuated in the SHR compared with the WKY. On the other hand, the pressor response to sympathetic activation due to the ERR was smaller at the age of 12 and 24 weeks than those at the age of 4 weeks. These results indicate that ERR is enhanced in the early stage of hypertension, and attenuated in the later stage of hypertension in the SHR. Abnormal ERR is involved in the sympathetic activation and the development of hypertension.<\/jats:p>","DOI":"10.3389\/fphys.2021.673950","type":"journal-article","created":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T17:04:49Z","timestamp":1622739889000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Dysregulation of the Excitatory Renal Reflex in the Sympathetic Activation of Spontaneously Hypertensive Rat"],"prefix":"10.3389","volume":"12","author":[{"given":"Chao","family":"Ye","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fen","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Xiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Li","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue-Hua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ming","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-Qing","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/s1054-8807(03)00135-2","article-title":"Temporal characteristics of cardiomyocyte hypertrophy in the spontaneously hypertensive rat.","volume":"13","author":"Bell","year":"2004","journal-title":"Cardiovasc. Pathol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1111\/apha.12718","article-title":"Normotension, hypertension and body fluid regulation: brain and kidney.","volume":"219","author":"Bie","year":"2017","journal-title":"Acta Physiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1111\/apha.12816","article-title":"Therapeutic value of renal denervation in cardiovascular disease?","volume":"220","author":"Carlstrom","year":"2017","journal-title":"Acta Physiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1113\/expphysiol.2010.054353","article-title":"AT1 receptors in paraventricular nucleus contribute to sympathetic activation and enhanced cardiac sympathetic afferent reflex in renovascular hypertensive rats.","volume":"96","author":"Chen","year":"2011","journal-title":"Exp. Physiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1111\/apha.12447","article-title":"Cardiac sympathetic afferent reflex and its implications for sympathetic activation in chronic heart failure and hypertension.","volume":"213","author":"Chen","year":"2015","journal-title":"Acta Physiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12264-019-00337-0","article-title":"Autonomic rregulation of the cardiovascular system: diseases, treatments, and novel approaches.","volume":"35","author":"Cheng","year":"2019","journal-title":"Neurosci. Bull."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e25","DOI":"10.1161\/HYPERTENSIONAHA.113.02439","article-title":"Sympathetic nervous system moves toward center stage in cardiovascular medicine: from Thomas Willis to resistant hypertension.","volume":"63","author":"Esler","year":"2014","journal-title":"Hypertension"},{"key":"B8","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1038\/gt.2011.145","article-title":"Artificial microRNA interference targeting AT1a receptors in paraventricular nucleus attenuates hypertension in rats.","volume":"19","author":"Fan","year":"2012","journal-title":"Gene Ther."},{"key":"B9","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1113\/expphysiol.2009.047332","article-title":"Therapeutic strategies for targeting excessive central sympathetic activation in human hypertension.","volume":"95","author":"Fisher","year":"2010","journal-title":"Exp. Physiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/0304-3959(83)90012-x","article-title":"Capsaicin and sensory neurones\u2013a review.","volume":"15","author":"Fitzgerald","year":"1983","journal-title":"Pain"},{"key":"B11","doi-asserted-by":"publisher","first-page":"R112","DOI":"10.1152\/ajpregu.00427.2014","article-title":"A novel method of selective ablation of afferent renal nerves by periaxonal application of capsaicin.","volume":"308","author":"Foss","year":"2015","journal-title":"Am. J. Physiol Regul. Integr. Comp. Physiol."},{"key":"B12","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s11906-016-0676-z","article-title":"Renal afferents.","volume":"18","author":"Frame","year":"2016","journal-title":"Curr. Hypertens. Rep."},{"key":"B13","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1385\/1-59259-850-1:003","article-title":"Congenic\/consomic models of hypertension.","volume":"108","author":"Graham","year":"2005","journal-title":"Methods Mol. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/j.jash.2016.02.015","article-title":"Evidence for a critical role of the sympathetic nervous system in hypertension.","volume":"10","author":"Grassi","year":"2016","journal-title":"J. Am. Soc. Hypertens."},{"key":"B15","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1161\/circresaha.116.303604","article-title":"The sympathetic nervous system alterations in human hypertension.","volume":"116","author":"Grassi","year":"2015","journal-title":"Circ. Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"F583","DOI":"10.1152\/ajprenal.00246.2015","article-title":"Renal denervation for the treatment of resistant hypertension: review and clinical perspective.","volume":"309","author":"Iliescu","year":"2015","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"E1682","DOI":"10.3390\/ijms18081682","article-title":"Sympathetic overactivity in chronic kidney disease: consequences and mechanisms.","volume":"18","author":"Kaur","year":"2017","journal-title":"Int. J. Mol. Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"R79","DOI":"10.1152\/ajpregu.00351.2014","article-title":"Role of renal sensory nerves in physiological and pathophysiological conditions.","volume":"308","author":"Kopp","year":"2015","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1161\/01.hyp.9.1.69","article-title":"Impaired renorenal reflexes in spontaneously hypertensive rats.","volume":"9","author":"Kopp","year":"1987","journal-title":"Hypertension"},{"key":"B20","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1161\/hypertensionaha.107.094649","article-title":"Differing pattern of sympathoexcitation in normal-weight and obesity-related hypertension.","volume":"50","author":"Lambert","year":"2007","journal-title":"Hypertension"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcad.2021.02.005","article-title":"The current status of renal denervation for the treatment of arterial hypertension.","author":"Lauder","year":"2021","journal-title":"Prog. Cardiovasc. Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1113\/expphysiol.2008.042036","article-title":"Role of TRPV1 channels in renal haemodynamics and function in Dahl salt-sensitive hypertensive rats.","volume":"93","author":"Li","year":"2008","journal-title":"Exp. Physiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/s00424-019-02346-4","article-title":"Afferent innervation of the ischemic kidney contributes to renal dysfunction in renovascular hypertensive rats.","volume":"472","author":"Lopes","year":"2020","journal-title":"Pflugers Arch."},{"key":"B24","doi-asserted-by":"publisher","first-page":"601237","DOI":"10.3389\/fphys.2020.601237","article-title":"Renal sensory activity regulates the \u03b3-aminobutyric acidergic inputs to the paraventricular nucleus of the hypothalamus in Goldblatt hypertension.","volume":"11","author":"Milanez","year":"2020","journal-title":"Front. Physiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1161\/01.hyp.0000256530.39695.a3","article-title":"Sympathetic hyperactivity in hypertensive chronic kidney disease patients is reduced during standard treatment.","volume":"49","author":"Neumann","year":"2007","journal-title":"Hypertension"},{"key":"B26","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1007\/s12264-019-00460-y","article-title":"Angiotensin type 1 receptors and superoxide anion production in hypothalamic paraventricular nucleus contribute to capsaicin-induced excitatory renal reflex and sympathetic activation.","volume":"36","author":"Qiu","year":"2020","journal-title":"Neurosci. Bull."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1698795","DOI":"10.1080\/20013078.2019.1698795","article-title":"MiR155-5p in adventitial fibroblasts-derived extracellular vesicles inhibits vascular smooth muscle cell proliferation via suppressing angiotensin-converting enzyme expression.","volume":"9","author":"Ren","year":"2020","journal-title":"J. Extracell. Vesicles"},{"key":"B28","doi-asserted-by":"publisher","first-page":"F606","DOI":"10.1152\/ajprenal.1990.258.3.F606","article-title":"Role of the kidney in primary hypertension: a renal transplantation study in rats.","volume":"258","author":"Rettig","year":"1990","journal-title":"Am. J. Physiol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"F197","DOI":"10.1152\/ajprenal.1989.257.2.F197","article-title":"Hypertension transmitted by kidneys from stroke-prone spontaneously hypertensive rats.","volume":"257","author":"Rettig","year":"1989","journal-title":"Am. J. Physiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1161\/hypertensionaha.111.187021","article-title":"Vascular remodeling in hypertension: mechanisms and treatment.","volume":"59","author":"Schiffrin","year":"2012","journal-title":"Hypertension"},{"key":"B31","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1007\/s40292-014-0056-1","article-title":"Role of the sympathetic nervous system in hypertension and hypertension-related cardiovascular disease.","volume":"21","author":"Seravalle","year":"2014","journal-title":"High Blood Press. Cardiovasc. Prev."},{"key":"B32","doi-asserted-by":"publisher","first-page":"e3074","DOI":"10.1038\/cddis.2017.470","article-title":"NLRP3 inflammasome activation contributes to VSMC phenotypic transformation and proliferation in hypertension.","volume":"8","author":"Sun","year":"2017","journal-title":"Cell Death. Dis."},{"key":"B33","first-page":"327","article-title":"Sympathetic nervous system and hypertension in diabetic patients.","volume":"13","author":"Vecchione","year":"2000","journal-title":"Diabetes Nutr. Metab."},{"key":"B34","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1038\/nrneph.2014.59","article-title":"Renal denervation\u2013implications for chronic kidney disease.","volume":"10","author":"Veelken","year":"2014","journal-title":"Nat. Rev. Nephrol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/j.jcin.2020.11.003","article-title":"Improved understanding of renal nerve anatomy: an opportunity to enhance denervation treatment of hypertension.","volume":"14","author":"Weber","year":"2021","journal-title":"JACC Cardiovasc. Interv."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1161\/hypertensionaha.112.198002","article-title":"Enhanced adipose afferent reflex contributes to sympathetic activation in diet-induced obesity hypertension.","volume":"60","author":"Xiong","year":"2012","journal-title":"Hypertension"},{"key":"B37","doi-asserted-by":"publisher","first-page":"H1103","DOI":"10.1152\/ajpheart.00862.2014","article-title":"Activation of afferent renal nerves modulates RVLM-projecting PVN neurons.","volume":"308","author":"Xu","year":"2015","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/s12264-019-00417-1","article-title":"Chemical stimulation of renal tissue induces sympathetic activation and pressor response via hypothalamic paraventricular nucleus.","volume":"36","author":"Ye","year":"2020","journal-title":"Neurosci. Bull."},{"key":"B39","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1113\/expphysiol.2008.046334","article-title":"Neurohumoral mechanisms in deoxycorticosterone acetate (DOCA)-salt hypertension in rats.","volume":"95","author":"Yemane","year":"2010","journal-title":"Exp. Physiol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1097\/hjh.0000000000000143","article-title":"Salusin-beta in rostral ventrolateral medulla increases sympathetic outflow and blood pressure via superoxide anions in hypertensive rats.","volume":"32","author":"Zhang","year":"2014","journal-title":"J. Hypertens."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1007\/s00424-020-02461-7","article-title":"Interleukin-1\u03b2 in hypothalamic paraventricular nucleus mediates excitatory renal reflex.","volume":"472","author":"Zheng","year":"2020","journal-title":"Pflugers Arch."},{"key":"B42","doi-asserted-by":"publisher","first-page":"144","DOI":"10.2174\/1573402114666181031141840","article-title":"Ablation of TRPV1 elevates nocturnal blood pressure in Western diet-fed mice.","volume":"15","author":"Zhong","year":"2019","journal-title":"Curr. Hypertens. Rev."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.673950\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T17:04:55Z","timestamp":1622739895000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.673950\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,3]]},"references-count":42,"alternative-id":["10.3389\/fphys.2021.673950"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2021.673950","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,3]]},"article-number":"673950"}}