OP014 Hydrogen sulfide induces relaxation independent of changes in smooth muscle cell calcium in rat small arteries

Abstract

Background and purpose Hydrogen sulfide (H2S) is an endogenously produced gas with many physiological functions including involvement in regulation of the blood pressure. The present study was designed to investigate the effect of H2S in small arteries and the mechanisms underlying H2S-induced vasodilation. Experimental approach Mesenteric and pulmonary small arteries from rats were isolated and mounted in microvascular myographs for isometric tension recordings. The endogenous production of H2S was blocked with enzyme inhibitors dl-propargylglycine (PPG) and amino-oxyacetate (AOA) with and without the presence of blockers of nitric oxide (NO) synthase (nitro- l -arginine) and cyclooxygenase (indomethacin). NaHS (a H2S donor) was applied in arteries with and without endothelium as well as in the presence of different blockers. Simultaneous measurements of intracellular calcium concentration and force were conducted by fura-2 AM fluorescence. Key results In mesenteric arteries acetylcholine (ACh)-induced vasodilation was reduced in the presence of PPG and AOA both in the absence and the presence of indomethacin and nitro- l -arginine. In pulmonary arteries, the combination of indomethacin and nitro- l -arginine inhibited ACh-induced vasodilation, and there was no further effect by adding PPG and AOA. Application of NaHS relaxed mesenteric arteries with an EC50 of 385 μM. Removing endothelium, inhibition of KATP-channels or NO synthase did not affect H2S-induced vasodilation in mesenteric or pulmonary arteries. Simultaneous measurements of calcium and relaxation revealed that NaHS induces relaxation without changes in smooth muscle calcium. Conclusions and implications H2S induces vasodilation in both rat mesenteric and pulmonary arteries, but is only involved in ACh-induced vasodilatation in rat mesenteric arteries. H2S-induced vasodilation was endothelium-independent and may involve desensitization of the contractile apparatus in the vascular smooth muscle.