Article

The baroreflex afferent pathway plays a critical role in H2S-mediated autonomic control of blood pressure regulation under physiological and hypertensive conditions

Ying Li1,2, Yan Feng1,3, Li Liu1, Xue Li1, Xin-yu Li1, Xun Sun1,3, Ke-xin Li1,3, Rong-rong Zha1,3, Hong-dan Wang1, Meng-di Zhang1,4, Xiong-xiong Fan1, Di Wu1, Yao Fan1, Hao-cheng Zhang1, Guo-fen Qiao1, Bai-yan Li1
1 Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, China
2 Department of Pharmacy, PLA Rocket Force Characteristic Medical Center, Beijing 100088, China
3 Department of Biomedical Engineering, Indiana University–Purdue University, Indianapolis, IN 46202, USA
4 Department of Physics, School of Science, Indiana University–Purdue University, Indianapolis, IN 46202, USA
Correspondence to: Bai-yan Li: liby@ems.hrbmu.edu.cn,
DOI: 10.1038/s41401-020-00549-5
Received: 23 June 2020
Accepted: 24 September 2020
Advance online: 5 November 2020

Abstract

Hydrogen sulfide (H2S), which is closely related to various cardiovascular disorders, lowers blood pressure (BP), but whether this action is mediated via the modification of baroreflex afferent function has not been elucidated. Therefore, the current study aimed to investigate the role of the baroreflex afferent pathway in H2S-mediated autonomic control of BP regulation. The results showed that baroreflex sensitivity (BRS) was increased by acute intravenous NaHS (a H2S donor) administration to renovascular hypertensive (RVH) and control rats. Molecular expression data also showed that the expression levels of critical enzymes related to H2S were aberrantly downregulated in the nodose ganglion (NG) and nucleus tractus solitarius (NTS) in RVH rats. A clear reduction in BP by the microinjection of NaHS or L-cysteine into the NG was confirmed in both RVH and control rats, and a less dramatic effect was observed in model rats. Furthermore, the beneficial effects of NaHS administered by chronic intraperitoneal infusion on dysregulated systolic blood pressure (SBP), cardiac parameters, and BRS were verified in RVH rats. Moreover, the increase in BRS was attributed to activation and upregulation of the ATP-sensitive potassium (KATP) channels Kir6.2 and SUR1, which are functionally expressed in the NG and NTS. In summary, H2S plays a crucial role in the autonomic control of BP regulation by improving baroreflex afferent function due at least in part to increased KATP channel expression in the baroreflex afferent pathway under physiological and hypertensive conditions.
Keywords: hydrogen sulfide; hydrogen sulfide synthase; blood pressure regulation; baroreflex afferent pathway; potassium channel; protein kinase

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