Elmoselhi A B, Grover A K
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Mol Cell Biochem. 1999 Dec;202(1-2):47-52. doi: 10.1023/a:1007034600527.
Endothelins (ETs) contract de-endothelialized rings from left descending coronary artery via ET(A) or ET(B) receptors. Here we test the hypothesis that the actions of EA(A) and ET(B) receptors are similar in their sensitivities to damage by hydrogen peroxide. In Ca2+-containing Krebs' solution, 100 nM of the ET(B) agonist IRL1620 produced contractions with significantly smaller force (17.6+/-1.7 mN) than 50 nM of the ET(A) + ET(B) agonist ET-1 (73.2+/-4.6 mN) (p < 0.05). In Ca2+-free solutions, the contractions due to both agents were significantly smaller (p < 0.05). Pretreating the tissues with peroxide inhibited the contractions produced by either agent. The IC50 values for peroxide were significantly higher (p < 0.05) using ET-1 (1.0+/-0.3 mM in Ca2+, 1.4+/-0.1 mM in Ca2+-free) than using IRL 1620 (0.32+/-0.08 in Ca2+, 0.25+/-0.01 mM in Ca2+-free). Pretreating microsomes isolated from the artery smooth muscle with up to 10 mM peroxide did not significantly affect 125I-ET-1 binding to ET(A) or ET(B) receptors (p > 0.05). In comparing the peroxide induced inactivation of the various processes in this artery and based on literature, we conclude that the actions of ET(A) may also involve a peroxide resistant Ca2+-independent pathway(s).
内皮素（ETs）通过ET(A)或ET(B)受体使左冠状动脉降支的去内皮环收缩。在此，我们检验了这样一个假设，即ET(A)和ET(B)受体的作用在对过氧化氢损伤的敏感性方面是相似的。在含Ca2+的Krebs溶液中，100 nM的ET(B)激动剂IRL1620产生的收缩力（17.6±1.7 mN）明显小于50 nM的ET(A)+ET(B)激动剂ET-1（73.2±4.6 mN）（p<0.05）。在无Ca2+的溶液中，两种药物引起的收缩均明显较小（p<0.05）。用过氧化氢预处理组织可抑制两种药物产生的收缩。使用ET-1时，过氧化氢的IC50值（在含Ca2+溶液中为1.0±0.3 mM，在无Ca2+溶液中为1.4±0.1 mM）明显高于使用IRL1620时（在含Ca2+溶液中为0.32±0.08 mM，在无Ca2+溶液中为0.25±0.01 mM）（p<0.05）。用高达10 mM的过氧化氢预处理从动脉平滑肌分离的微粒体，对125I-ET-1与ET(A)或ET(B)受体的结合没有显著影响（p>0.05）。在比较过氧化氢对该动脉各种过程的诱导失活作用并参考文献后，我们得出结论，ET(A)的作用可能还涉及一条对过氧化氢有抗性的不依赖Ca2+的途径。
