Hydrogen sulfide-induced relaxation of resistance mesenteric artery beds of rats

Abstract

Hydrogen sulfide (H2S) has been shown recently to function as an important gasotransmitter. The present study investigated the vascular effects of H2S, both exogenously applied and endogenously generated, on resistance mesenteric arteries of rats and the underlying mechanisms. Both H2S and NaHS evoked concentration-dependent relaxation of in vitro perfused rat mesenteric artery beds (MAB). The sensitivity of MAB to H2S (EC50, 25.2 +/- 3.6 microM) was about fivefold higher than that of rat aortic tissues. Removal of endothelium or coapplication of charybdotoxin and apamin to endothelium-intact MAB significantly reduced the vasorelaxation effects of H2S. The H2S-induced relaxation of MAB was partially mediated by ATP-sensitive K+ (KATP) channel activity in vascular smooth muscle cells. Pinacidil (EC50, 1.7 +/- 0.1 microM, n=6) mimicked, but glibenclamide (10 microM, n=6) suppressed, the vasorelaxant effect of H2S. KATP channel currents in isolated mesenteric artery smooth muscle cells were significantly augmented by H2S. L-cysteine, a substrate of cystathionine-gamma-lyase (CSE), at 1 mM increased endogenous H2S production by sixfold in rat mesenteric artery tissues and decreased contractility of MAB. DL-propargylglycine (a blocker of CSE) at 10 microM abolished L-cysteine-dependent increase in H2S production and relaxation of MAB. Our results demonstrated a tissue-specific relaxant response of resistance arteries to H2S. The stimulation of KATP channels in vascular smooth muscle cells and charybdotoxin/apamin-sensitive K+ channels in vascular endothelium by H2S represents important cellular mechanisms for H2S effect on MAB. Our study also demonstrated that endogenous CSE can generate sufficient H2S from exogenous L-cysteine to cause vasodilation. Future studies are merited to investigate direct contribution of endogenous H2S to regulation of vascular tone.

Dysregulation of hydrogen sulphide metabolism impairs oviductal transport of embryos

“…In the present study, we demonstrated that both CSE and CBS were expressed primarily in the human oviduct epithelium. H 2 S has been shown to cause relaxation of arterial blood vessels 2,21,22 , small bronchial rings [23][24][25] , human corpus cavernosum 7 , rat vas deferens 11 , and gastrointestinal and urogenital smooth muscle 26 . The human fallopian tube is capable of synthesizing H 2 S. In our in vitro experiments, the production of H 2 S also relaxed the spontaneous contraction of the human oviduct, which suggests that an endogenous H 2 S relaxation system functionally exists in the fallopian tube.…”

Hydrogen Sulfide and Endothelial Dysfunction: Relationship with Nitric Oxide

“…The vasorelaxing action of NaHS, administrated at concentrations ranging from 50 µM to 100 µM, has been observed in rat aorta and hepatic artery [96,97], as well as in resistance mesenteric arteries [21], gastric artery and gastric mucosal circulation [98], cerebral arterioles and artery [99,100], pulmonary artery [101], and coronary artery [102]. Since NaHS is five-to-nine fold more potent in relaxing mesenteric arteries than thoracic aorta and pulmonary artery (EC 50 25 µM vs. 125 µM and 233 µM, respectively), it has been proposed as a key regulator of peripheral resistance arteries and, therefore, of blood pressure [15].…”

H2S in the Vasculature: Controversy of Mechanisms in Physiology, Pathology and Beyond

“…An increasing number of reports show that contribution of H 2 S depends on vascular beds tested (e.g., aorta vs. mesenteric artery), vessel size (conduit vs. resistant) [5], endothelium (intact vs. denuded), gender [19], duration, concentration, and rate of administration of H 2 S or its donor (e.g., NaHS). Other factors influencing H 2 S response in the vasculature are model organisms and the preconstriction methods (e.g., phenylephrine, U46619) [20,21].…”

“…The exact mechanism of how H 2 S contributes to this process remains elusive. While the major source of H 2 S in plasma is likely produced by VSMCs [35], ECs have been recognized to contribute to the vascular effects stimulated by H 2 S [36]. This divergence could contribute to the biphasic phenotypes observed with H 2 S in vascular signaling (proliferative/antigenic nature vs. atheroprotective nature).…”

“…In the vasculature, H 2 S is produced in both the vascular endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) by CSE [2,[4][5][6][7]. CSE is a pyridoxal 5'-phosphate-dependent cytosolic enzyme and CSE activity is regulated by intracellular Ca 2+ concentrations [8].…”