Department of Pediatrics, Peking University First Hospital, Beijing, China.
Acta Pharmacol Sin. 2011 Apr;32(4):456-64. doi: 10.1038/aps.2011.9.
To compare the vasorelaxing effects of hydrogen sulfide (H(2)S) on isolated aortic and pulmonary artery rings and to determine their action mechanisms.
H(2)S-induced vasorelaxation of isolated rat aortic versus pulmonary artery rings under 95% O(2) and 5% CO(2) was analyzed. The expression of cystathinonine gamma-lyase (CSE), cystathionine beta synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3MST), SUR2B and Kir6.1 was examined.
NaHS caused vasorelaxation of rat aortic and pulmonary artery rings in a dose-dependent manner. NaHS dilated aortic rings to a greater extent (16.4%, 38.4%, 64.1%, 84.3%, and 95.9% at concentrations of 50, 100, 200, 500, and 1000 μmol/L, respectively) than pulmonary artery rings (10.1%, 22.2%, 50.6%, 73.6%, and 84.6% at concentrations of 50, 100, 200, 500 and 1000 μmol/L, respectively). The EC(50) of the vasorelaxant effect for aortic rings was 152.17 μmol/L, whereas the EC(50) for pulmonary artery rings was 233.65 μmol/L. The vasorelaxing effect of H(2)S was markedly blocked b y cellular and mitochondrial membrane K(ATP) channel blockers in aortic rings (P<0.01). In contrast, only the cellular membrane K(ATP) channel blocker inhibited H(2)S-induced vasorelaxation in pulmonary artery rings. SUR2B mRNA and protein expression was higher in aortic rings than in pulmonary artery rings. Cystathinonine gamma-lyase (CSE) but not cystathionine beta synthase (CBS) expression in aortic rings was higher than in pulmonary artery rings. 3-Mercapto pyruvate sulfurtransferase (3MST) mRNA was lower in aortic rings than in pulmonary artery rings.
The vasorelaxing effect of H(2)S on isolated aortic rings was more pronounced than the effect on pulmonary artery rings at specific concentrations, which might be associated with increased expression of the K(ATP) channel subunit SUR2B.
比较硫化氢(H(2)S)对离体主动脉和肺动脉环的血管舒张作用,并确定其作用机制。
分析 95%O(2)和 5%CO(2)下 H(2)S 诱导的分离大鼠主动脉和肺动脉环的血管舒张作用。检测胱硫醚γ-裂解酶(CSE)、胱硫醚β-合酶(CBS)、3-巯基丙酮酸硫转移酶(3MST)、SUR2B 和 Kir6.1 的表达。
NaHS 引起大鼠主动脉和肺动脉环呈剂量依赖性血管舒张。NaHS 扩张主动脉环的程度大于肺动脉环(浓度为 50、100、200、500 和 1000μmol/L 时分别为 16.4%、38.4%、64.1%、84.3%和 95.9%;浓度为 50、100、200、500 和 1000μmol/L 时分别为 10.1%、22.2%、50.6%、73.6%和 84.6%)。主动脉环血管舒张作用的 EC(50)为 152.17μmol/L,而肺动脉环的 EC(50)为 233.65μmol/L。H(2)S 的血管舒张作用在主动脉环中被细胞和线粒体膜 K(ATP)通道阻滞剂明显阻断(P<0.01)。相比之下,只有细胞膜 K(ATP)通道阻滞剂抑制了肺动脉环中 H(2)S 诱导的血管舒张作用。SUR2B mRNA 和蛋白表达在主动脉环中高于肺动脉环。与肺动脉环相比,主动脉环中胱硫醚γ-裂解酶(CSE)的表达高于胱硫醚β-合酶(CBS)。3-巯基丙酮酸硫转移酶(3MST)mRNA 在主动脉环中的表达低于肺动脉环。
在特定浓度下,H(2)S 对分离的主动脉环的血管舒张作用强于对肺动脉环的作用,这可能与 K(ATP)通道亚基 SUR2B 的表达增加有关。