Endogenous Hydrogen Sulfide Enhances Carotid Sinus Baroreceptor Sensitivity by Activating the Transient Receptor Potential Cation Channel Subfamily V Member 1 (TRPV1) Channel

Abstract

BackgroundWe aimed to investigate the regulatory effects of hydrogen sulfide (H2S) on carotid sinus baroreceptor sensitivity and its mechanisms.Methods and ResultsMale Wistar‐Kyoto rats and spontaneously hypertensive rats (SHRs) were used in the experiment and were given an H2S donor or a cystathionine‐β‐synthase inhibitor, hydroxylamine, for 8 weeks. Systolic blood pressure and the cystathionine‐β‐synthase/H2S pathway in carotid sinus were detected. Carotid sinus baroreceptor sensitivity and the functional curve of the carotid baroreceptor were analyzed using the isolated carotid sinus perfusion technique. Effects of H2S on transient receptor potential cation channel subfamily V member 1 (TRPV1) expression and S‐sulfhydration were detected. In SHRs, systolic blood pressure was markedly increased, but the cystathionine‐β‐synthase/H2S pathway in the carotid sinus was downregulated in comparison to that of Wistar‐Kyoto rats. Carotid sinus baroreceptor sensitivity in SHRs was reduced, demonstrated by the right and upward shift of the functional curve of the carotid baroreceptor. Meanwhile, the downregulation of TRPV1 protein was demonstrated in the carotid sinus; however, H2S reduced systolic blood pressure but enhanced carotid sinus baroreceptor sensitivity in SHRs, along with TRPV1 upregulation in the carotid sinus. In contrast, hydroxylamine significantly increased the systolic blood pressure of Wistar‐Kyoto rats, along with decreased carotid sinus baroreceptor sensitivity and reduced TRPV1 protein expression in the carotid sinus. Furthermore, H2S‐induced enhancement of carotid sinus baroreceptor sensitivity of SHRs could be amplified by capsaicin but reduced by capsazepine. Moreover, H2S facilitated S‐sulfhydration of TRPV1 protein in the carotid sinus of SHRs and Wistar‐Kyoto rats.ConclusionsH2S regulated blood pressure via an increase in TRPV1 protein expression and its activity to enhance carotid sinus baroreceptor sensitivity.

Increased Abundance of Lactobacillales in the Colon of Beta-Adrenergic Receptor Knock Out Mouse Is Associated With Increased Gut Bacterial Production of Short Chain Fatty Acids and Reduced IL17 Expression in Circulating CD4+ Immune Cells

“…We also observed a depletion of Eubacteriaceae and Peptococcaceae in the order of Clostridiales and in the phyla of Firmicutes, in our b1.b2 Adr KO mice. These strains are largely considered to be beneficial, with Peptococcaceae a sulfate-reducing bacteria (Petzsch et al, 2015 ), a property suggested to be important in regulation of BP (Ahmad et al, 2012 ; Yu et al, 2017 ). Similarly, we saw a reduction in Bilophila in the b1.b2 Adr KO mice, which are, however considered to be largely pathogenic, which may be related to reduced presence of hydrogen sulfide (da Silva et al, 2008 ).…”

H2S-Induced Sulfhydration: Biological Function and Detection Methodology

“…Sun et al found that H 2 S could increase intracellular cGMP level via sulfhydrate phosphodiesterase 5A to inhibit the cGMP degradation ( Sun et al, 2017 ). Moreover, Yu et al (2017) demonstrated that S -sulfhydration of TRPV1 by CBS-derived H 2 S in carotid sinus facilitated carotid sinus baroreceptor sensitivity to participated the control of blood pressure.…”

ASIC2 Synergizes with TRPV1 in the Mechano-Electrical Transduction of Arterial Baroreceptors

“…In recent years, it has been suggested that the arterial baroreceptor reflex participates in the long-term regulation of blood pressure [34,35], and pressure-dependent discharges from the carotid sinus nerve are significantly reduced in correlation with a decrease in TRPV1 protein expression in baroreceptors from spontaneously-hypertensive rats [36]. In addition, symptoms of high blood pressure and a marked decline in aortic nerve activity have been found in ASIC2-knockout mice [3].…”