硫化氢收缩大鼠脑动脉

OBJECTIVE This study was designed to examine that vasoconstrictive effect of hydrogen sulfide, a new endogenous mediator on rat cerebral artery. METHODS NaHS was used as the donor of H2S. The vasoconstrictive effect of NaHS on rat cerebral artery was measured by wire myograph. H2S production was measured by sulfur electrode. RESULTS NaHS induced a concentration-dependently vasoconstriction on rat cerebral artery. Salbutamol, a β-adrenoceptor agonists, and forskolin, a selective adenylyl cyclase activator produced stronger vasoconstriction caused by NaHS on rat cerebral artery, respectively. Pretreatment with NaHS also significantly attenuated the vasorelaxant effect of salbutamol and forskolin on 5-HT precontracted rat cerebral artery. Rauwolscine, a α2-adrenoceptor agonists, and 8B-cAMP, a cell permeable analog of cAMP produced weaker vasoconstriction caused by NaHS on rat cerebral artery, respectively. However, NaHS produced stronger vasoconstriction in the presence of L-NAME, a nitric oxide synthase inhibitor, or in the endothelium-denuded rat cerebral artery. NaHS also produced weaker vasodilation caused by forskolin in the presence of L-NAME but not in endothelium-denuded rat cerebral artery. Blockade of ATP-sensitive potassium channels with glibenclamide failed to attenuate the vasoconstriction induced by NaHS. Nifedpine, a specific L-type Ca2+ channel inhibitor, reduced the vasoconstriction caused by NaHS while Bay K 8644, a specific L-type Ca2+ channel agonist, failed to attenuate the vasoconstriction caused by NaHS on rat cerebral artery . In HEPES and Krebs buffers, the HCO3- dependent effect was specific to H2S. Blockade of anion exchanger-2 activity with DIDS or with HCO3- free solution abolished the vasoconstrictive effect of NaHS. Tiron,a ROS scavenger, produced weaker vasoconstriction caused by NaHS on rat cerebral artery.The plasma H2S concentration and H2S production in brain tissues both decreased in SHR compared to SD rats. CONCLUSION H2S contracts rat cerebral artery. The vasoconstrictive effect of H2S may be involved in the adenyly cyclase/cAMP pathway. H2S also stimulates anion exchanger to transport extracellular HCO3- in exchange for intracellular superoxide anions which may further inactivate NO to induce vasoconstriction.