Vasoconstrictive effect of hydrogen sulfide involves downregulation of cAMP in vascular smooth muscle cells

Lim JJ, Liu YH, Khin ES, Bian JS. Vasoconstrictive effect of hydrogen sulfide involves downregulation of cAMP in vascular smooth muscle cells. Am J Physiol Cell Physiol 295: C1261-C1270, 2008. First published September 11, 2008; doi: 10.1152/ajpcell.00195.2008.- Hydrogen sulfide (H2S), a new endogenous mediator, produces both vasorelaxation and vasoconstriction. This study was designed to examine whether cAMP mediates the vasoconstrictive effect of H2S. We found that NaHS at a concentration range of 10-100 mu M (yields similar to 3-30 mu M H2S) concentration- dependently reversed the vasodilation caused by isoprenaline and salbutamol, two beta-adrenoceptor agonists, and forskolin, a selective adenylyl cyclase activator, in phenylephrine-precontracted rat aortic rings. Pretreatment with NaHS (10-100 mu M) for 5 min also significantly attenuated the vasorelaxant effect of salbutamol and forskolin. More importantly, NaHS (5-100 mu M) significantly reversed forskolin-induced cAMP accumulation in vascular smooth muscle cells. However, NaHS produced significant, but weaker, vasoconstriction in the presence of NG-nitro-L-argininemethyl ester (100 mu M), a nitric oxide synthase inhibitor, or in endothelium-denuded aortic rings. Blockade of ATP-sensitive potassium channels with glibenclamide (10 mu M) failed to attenuate the vasoconstriction induced by H2S. Taken together, we demonstrated for the first time that the vasoconstrictive effect of H2S involves the adenyly cyclase/cAMP pathway.