Ferrer M, Encabo A, Marín J, Balfagón G
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
Eur J Pharmacol. 1994 Jun 2;258(1-2):103-10. doi: 10.1016/0014-2999(94)90062-0.
The objective of this study was to analyze the effect of chronic treatment of rabbits for 4, 8 and 12 weeks with the anabolic steroid, nandrolone, on the contractile responses induced by different agents in segments of thoracic aorta and mesenteric and femoral arteries. In the three types of arteries, the contractions elicited by noradrenaline, 5-hydroxytryptamine and angiotensin II were increased by endothelium removal. The treatment reduced the contractions elicited by the three agents (mainly those caused by 5-hydroxytryptamine) in aorta, and only those caused by 5-hydroxytryptamine in mesenteric arteries. Ca(2+)-free medium containing 0.1 mM ethylene glycol bis (beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA) reduced the responses elicited by 1 microM noradrenaline, 10 microM 5-hydroxytryptamine and 0.1 microM angiotensin II in aorta segments from control rabbits. Addition of CaCl2 to this medium restored the initial responses elicited by the three agents in normal medium, both in arteries from control and treated rabbits. In aorta, the contractions elicited by phorbol 12,13-dibutyrate (PDB), an activator of protein kinase C, were reduced by the treatment. Staurosporine, an inhibitor of protein kinase C, reduced the responses evoked by PDB. Likewise, the contractions caused by noradrenaline, 5-hydroxytryptamine and especially by angiotensin II were also reduced by staurosporine. These results suggest that the thoracic aorta is the most affected by the treatment, and that the reduction of contractile responses appears to be due to changes in protein kinase C activity and/or in a mechanism situated beyond protein kinase C activation.
本研究的目的是分析用合成代谢类固醇诺龙对兔子进行4周、8周和12周的长期治疗，对胸主动脉、肠系膜动脉和股动脉节段中不同药物诱导的收缩反应的影响。在这三种类型的动脉中，去甲肾上腺素、5-羟色胺和血管紧张素II引起的收缩在去除内皮后增强。该治疗减少了主动脉中这三种药物引起的收缩（主要是5-羟色胺引起的收缩），而在肠系膜动脉中仅减少了5-羟色胺引起的收缩。含有0.1 mM乙二醇双（β-氨基乙基醚）-N,N'-四乙酸（EGTA）的无钙培养基降低了对照兔子主动脉节段中1 μM去甲肾上腺素、10 μM 5-羟色胺和0.1 μM血管紧张素II引起的反应。向该培养基中添加氯化钙可恢复对照和治疗兔子动脉中正常培养基中这三种药物最初引起的反应。在主动脉中，蛋白激酶C激活剂佛波醇12,13-二丁酸酯（PDB）引起的收缩因治疗而减少。蛋白激酶C抑制剂星形孢菌素降低了PDB引起的反应。同样，去甲肾上腺素、5-羟色胺尤其是血管紧张素II引起的收缩也被星形孢菌素降低。这些结果表明胸主动脉受治疗影响最大，收缩反应的降低似乎是由于蛋白激酶C活性的变化和/或蛋白激酶C激活之外的机制的变化。
