Received: 16 October 2021 Revised: six December 2021 Accepted: 14 December 2021 DOI: ten.1111/cns.
Es/10.3389/ fcimb.2022.1015957/fullsupplementary-material
Received: 16 October 2021 Revised: six December 2021 Accepted: 14 December 2021 DOI: 10.1111/cns.||ORIGINAL ARTICLEBradykinin-mediated estrogen-dependent depressor response by direct activation of female-specific distribution of myelinated Ah-type baroreceptor neurons in ratsKe-Xin Li1| Yan Feng1| Xiong-Xiong Fan1| Xun Sun1| Ying Li1| Di Wu1| Li Liu1| Chang-Peng Cui1| Xue Xiong1| Hu-Die Li1| Meng Zhou1| Hai-Lan Ma1| Yang Liu2| Rong Zhang1| Bai-Yan Li1 Department of Pharmacology (StateProvince Essential Laboratories of BiomedicinePharmaceutics of China, and Important Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Healthcare University, Harbin, China two Department of clinical Laboratory, The 1st Affiliated Hospital of Dalian Healthcare University, Dalian, ChinaAbstractAim: To understand the direct impact of bradykinin in autonomic control of circulation by way of baroreflex afferent pathway. Strategies: The imply arterial pressure (MAP) was monitored when bradykinin and its agonists have been applied through nodose (NG) microinjection, the expression of bradykinin receptors (BRs) in the NG (1st-order) and nucleus tractus solitarius (NTS, 2nd-order) have been tested in adult male, age-matched female, and ovariectomized rats beneath physiological and hypertensive situations. Furthermore, bradykinin-induced depolarization was also tested in identified baroreceptor and baroreceptive neurons applying whole-cell patch-clamp technique. Outcomes: Under physiological situation, bradykinin-induced dose- and estrogendependent reductions of MAP with lower estimated EC50 in females. B2R agonist mediated far more dramatic MAP reduction with long-lasting impact compared with B1R activation. These functional observations have been consistent with all the molecular and immunostaining evidences. Nonetheless, under hypertensive condition, the MAP reduction was considerably significantly less dramatic in N’-Nitro-L-Arginine-methyl ester (L-NAME) induced secondary and spontaneous hypertension rats in males compared with female rats. Electrophysiological data showed that bradykinin-elicited concentration-dependent membrane depolarization with discharges for the duration of initial phase in identified myelinated Ah-types baroreceptor neurons, not myelinated A-types; while, larger concentration of bradykinin was necessary for depolarization of unmyelinated C-types without the need of initial discharges.SHH Protein web Conclusion: These datasets have demonstrated for the first time that bradykinin mediates direct activation of baroreflex afferent function to trigger estrogen-dependent depressor response, that is due primarily to the direct activation/neuroexcitation of female-specific myelinated Ah-type baroreceptor neurons major to a sexualCorrespondence Bai-Yan Li and Rong Zhang, Division of Pharmacology, Harbin Medical University, 157 Baojian Road, Harbin 150081, China.Creatine kinase M-type/CKM Protein Storage & Stability Emails: liby@ems.PMID:23439434 hrbmu.edu.cn (B.-Y. L.); rongzhang77@163 (R. Z.) Funding facts National Organic Science Foundation of China, Grant/Award Quantity: 81573431, 81903599, 81971326 andKe-Xin Li, Yan Feng, Xiong-Xiong Fan contributed equally to this operate.That is an open access write-up beneath the terms with the Inventive Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original perform is adequately cited. 2021 The Authors. CNS Neuroscience Therapeutics published by John Wiley Sons Ltd. CNS Neurosci Ther. 2022;28:43547. wileyonlinelibrary/journal/.
