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

Acta Pharmacol Sin. 2021 Jun;42(6):898-908. doi: 10.1038/s41401-020-00549-5. Epub 2020 Nov 5.

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: baroreflex afferent pathway; blood pressure regulation; hydrogen sulfide; hydrogen sulfide synthase; potassium channel; protein kinase.

MeSH terms

  • Afferent Pathways / metabolism*
  • Animals
  • Antihypertensive Agents / pharmacology
  • Baroreflex / drug effects
  • Baroreflex / physiology*
  • Blood Pressure / drug effects
  • Blood Pressure / physiology*
  • Cardiotonic Agents / pharmacology
  • Cystathionine beta-Synthase / metabolism
  • Cystathionine gamma-Lyase / metabolism
  • Hydrogen Sulfide / metabolism*
  • Hydrogen Sulfide / pharmacology
  • Hypertension / drug therapy
  • Hypertension / physiopathology*
  • Male
  • Nodose Ganglion / drug effects
  • Nodose Ganglion / enzymology
  • Nodose Ganglion / metabolism
  • Potassium Channels, Inwardly Rectifying / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Solitary Nucleus / drug effects
  • Solitary Nucleus / enzymology
  • Solitary Nucleus / metabolism
  • Sulfides / pharmacology
  • Sulfonylurea Receptors / metabolism
  • Sulfurtransferases / metabolism

Substances

  • Abcc8 protein, rat
  • Antihypertensive Agents
  • Cardiotonic Agents
  • Kir6.2 channel
  • Potassium Channels, Inwardly Rectifying
  • Sulfides
  • Sulfonylurea Receptors
  • Sulfurtransferases
  • 3-mercaptopyruvate sulphurtransferase
  • Cystathionine beta-Synthase
  • Cystathionine gamma-Lyase
  • sodium bisulfide
  • Hydrogen Sulfide