Brizzolara-Gourdie A, Webb J G
Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Charleston 29425-2551, USA.
J Pharmacol Exp Ther. 1997 Apr;281(1):354-9.
We previously observed an effect of the Ca++-mobilizing peptide, angiotensin II (ANG II), to potentiate agonist-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) formation in rat cultured aortic smooth muscle cells. Consequently, it was postulated that the relaxant effects of dilator agents that act through cAMP formation would be enhanced in the presence of ANG II. To test this idea, we examined the influence of ANG II on agonist-induced relaxation of rat isolated aortic rings. Angiotensin II (0.1 microM) evoked a transient increase in the tone of KCI (30 mM)-precontracted aortae that returned to the original level of induced tension after about 20 min. Subsequent application of isoproterenol caused a concentration-dependent relaxation that was significantly greater in preparations pretreated with ANG II than in time-matched controls. Similarly, isoproterenol-induced relaxations of aortae precontracted with either phenylephrine (1 microM) or endothelin 1 (3 nM) were also augmented after ANG II treatment. The principal action of ANG II was to enhance the maximal relaxation evoked by isoproterenol without affecting the EC50 value, irrespective of the contractile agent used. This potentiating effect of ANG II was not specific for beta adrenoceptor-mediated relaxation because the relaxant response to iloprost, a prostaglandin I2 analog, was also increased after ANG II treatment. The effect of ANG II to enhance isoproterenol-induced relaxation was maintained in endothelium-denuded preparations. However, ANG II did not enhance the relaxation of vessels evoked through either the direct elevation of cAMP levels by dibutyryl cAMP or the stimulation of cyclic 3',5'-guanosine monophosphate formation by sodium nitroprusside. The data indicate that exposure of rat aortae to the constrictor peptide ANG II enhances the vasodilation of these blood vessels by agonists that stimulate cAMP formation. Such cross-talk between constrictor and dilator pathways could represent an important mechanism in the modulation of vascular tone.
我们之前观察到钙离子动员肽血管紧张素II（ANG II）可增强激动剂刺激的大鼠培养主动脉平滑肌细胞中3',5'-环磷酸腺苷（cAMP）的生成。因此，有人推测在ANG II存在的情况下，通过cAMP生成起作用的扩张剂的舒张作用会增强。为了验证这一想法，我们研究了ANG II对激动剂诱导的大鼠离体主动脉环舒张的影响。血管紧张素II（0.1微摩尔/升）引起氯化钾（30毫摩尔/升）预收缩主动脉张力短暂升高，约20分钟后恢复到诱导张力的原始水平。随后应用异丙肾上腺素引起浓度依赖性舒张，在经ANG II预处理的标本中，舒张作用明显大于时间匹配的对照组。同样，用去氧肾上腺素（1微摩尔/升）或内皮素1（3纳摩尔/升）预收缩的主动脉，经ANG II处理后，异丙肾上腺素诱导的舒张作用也增强。无论使用何种收缩剂，ANG II的主要作用是增强异丙肾上腺素引起的最大舒张，而不影响半数有效浓度（EC50）值。ANG II的这种增强作用并非β肾上腺素能受体介导的舒张所特有，因为经ANG II处理后，对前列环素I2类似物伊洛前列素的舒张反应也增强。ANG II增强异丙肾上腺素诱导舒张的作用在内皮剥脱的标本中依然存在。然而，ANG II并未增强通过二丁酰cAMP直接升高cAMP水平或硝普钠刺激环磷酸鸟苷生成所引起的血管舒张。数据表明，大鼠主动脉暴露于收缩肽ANG II可增强激动剂刺激cAMP生成所引起的这些血管的舒张。收缩和舒张途径之间的这种相互作用可能是调节血管张力的重要机制。
