Bauersachs J, Fraccarollo D, Galuppo P, Widder J, Ertl G
Medizinische Klinik der Julius-Maximilians-Universität Würzburg and II. Medizinische Klinik, Universitätsklinikum Mannheim, Mannheim, Germany.
Cardiovasc Res. 2000 Jul;47(1):142-9. doi: 10.1016/s0008-6363(00)00083-3.
To elucidate the effect of selective endothelin ET(A)- and mixed ET(A/B)-receptor antagonists on endothelial vasomotor dysfunction in rats with heart failure after myocardial infarction (MI).
Vasoreactivity and superoxide anion formation were determined in aortic rings from Wistar rats 12 weeks after extensive MI (>46% of left ventricle) compared to sham-operated animals. Rats were either treated with the selective ET(A)-receptor antagonist LU 135252 (30 mg/kg/day), the mixed ET(A/B)-receptor antagonist Bosentan (100 mg/kg/day) or placebo.
In MI rats, the concentration-response curve of the endothelium-dependent, nitric oxide-mediated relaxation induced by acetylcholine was significantly shifted to the right and the maximum relaxation was attenuated. Long-term treatment with both ET antagonists significantly improved acetylcholine-induced relaxation in MI rats. LU 135252 was more effective than Bosentan. Endothelium-independent relaxations induced by sodium nitroprusside as well as endothelin- and phenylephrine-induced contractions were similar in all groups of rats. Plasma renin activity and aortic superoxide formation, which were enhanced in rats with heart failure, were normalized by LU 135252, but not by Bosentan treatment.
Long-term treatment with ET-receptor antagonists improves endothelial vasomotor dysfunction in rats with chronic MI. This mechanism may essentially contribute to the beneficial effects of ET receptor blockade in heart failure.
阐明选择性内皮素ET(A)受体拮抗剂和混合性ET(A/B)受体拮抗剂对心肌梗死（MI）后心力衰竭大鼠内皮血管舒缩功能障碍的影响。
与假手术动物相比，在广泛MI（左心室>46%）12周后的Wistar大鼠主动脉环中测定血管反应性和超氧阴离子生成。大鼠分别接受选择性ET(A)受体拮抗剂LU 135252（30毫克/千克/天）、混合性ET(A/B)受体拮抗剂波生坦（100毫克/千克/天）或安慰剂治疗。
在MI大鼠中，乙酰胆碱诱导的内皮依赖性、一氧化氮介导的舒张浓度-反应曲线显著右移，最大舒张减弱。两种ET拮抗剂长期治疗均显著改善MI大鼠乙酰胆碱诱导的舒张。LU 135252比波生坦更有效。硝普钠诱导的非内皮依赖性舒张以及内皮素和去氧肾上腺素诱导的收缩在所有大鼠组中相似。心力衰竭大鼠中增强的血浆肾素活性和主动脉超氧生成通过LU 135252恢复正常，但波生坦治疗未使其恢复正常化。
ET受体拮抗剂长期治疗可改善慢性MI大鼠的内皮血管舒缩功能障碍。这一机制可能是ET受体阻断在心力衰竭中产生有益作用的重要原因。
