Hydrogen sulphide (H2S) attenuates responses mediated by endothelium-derived hyperpolarising factor (EDHF) in rat mesenteric small arteries

Maqdad M Taaqi, Jamila F Hussain, William R Dunn
University of Nottingham, Nottingham/Nottinghamshire, United Kingdom

Hydrogen Sulphide (H2S) causes two different effects in blood vessels. At high concentrations (>200μM) it causes vasorelaxation, by activating KATP channels, while at low concentrations (<100μM) it has been shown to attenuate endothelium-dependent responses in the rat aorta, by forming an inactive complex with nitric oxide (NO), to result in vasoconstriction. This latter mechanism has been implicated in the pressor response observed with low doses of H2S given to anaesthetized rats (Ali et al, 2006, Br J Pharmacol, 149, 625-634). Small arteries are more important determinants of vascular resistance than the aorta, and in these vessels endothelium-dependent responses are mediated by both NO and endothelium-derived hyperpolarising factor (EDHF). The present study, examined the effect of H2S on responses mediated by either NO or EDHF in rat mesenteric small arteries.

Male Wistar rats (200-250g) were killed by stunning and bleeding. The mesenteric bed was removed and arteries were dissected and mounted on a pressure myograph and held at a pressure of 30mmHg. Arteries were pre-contracted with U46619 to reduce diameter by 50-60%. Thereafter, responses to ACh were generated in the absence and presence of H2S (30μM). The effects of H2S (30μM) on ACh-induced vasodilatation were also assessed in the presence of the NO synthase inhibitor L-NAME (100μM), or after reducing artery diameter using raised extracellular potassium chloride (KCl) (45mM)

ACh caused a concentration-dependent vasodilatation of pressurised arteries. Under control conditions, H2S attenuated the maximum vasodilatation produced by ACh. When vessels were pre-incubated with L-NAME, H2S significantly reduced the sensitivity of responses to ACh (*p < 0.05, 2-way ANOVA). In contrast, in vessels pre-contracted with KCl, the concentration-dependent vasodilatation induced by ACh was unaffected by H2S (Table 1).

Responses to ACh mediated by EDHF (obtained in the presence of L-NAME), were attenuated by a low concentration of H2S, while those mediated by NO (obtained in the presence of raised extracellular KCl) were unaffected. These observations suggest a selective inhibitory effect of H2S on EDHF-mediated responses in small mesenteric arteries. Attenuating the release/action of EDHF may underlie the pressor response observed in response to H2S in vivo.