Henrion D, Laher I, Laporte R, Bevan J A
Department of Pharmacology, University of Vermont, College of Medicine, Burlington.
J Pharmacol Exp Ther. 1992 Jun;261(3):835-40.
We investigated whether the enhanced contractile response to norepinephrine caused by a subthreshold concentration of angiotensin II was associated with an increased 45Ca++ influx or net uptake. Rabbit facial artery segments were mounted isometrically to measure the 45Ca++ influx and net uptake in response to norepinephrine. The contractile response to norepinephrine (3 microM) in the presence of angiotensin II (0.1 nM) was 149.5 +/- 7.4% of control. This response amplification was not associated with changes in norepinephrine-induced 45Ca++ influx or net uptake. Angiotensin II also potentiated the contractile response to caffeine obtained in a Ca(++)-free buffer containing ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid (2 mM) to 148.0 +/- 4.8% of control. In both cases, the amplification was prevented by pretreatment with either staurosporine (10 nM) or calphostin C (100 nM), two inhibitors of protein kinase C. We conclude that angiotensin II potentiation of norepinephrine-induced vascular tone occurs in the absence of changes in stimulated Ca++ entry. This potentiation may be due to an increase in intracellular sensitivity to Ca++, possibly mediated by protein kinase C.
我们研究了由亚阈值浓度的血管紧张素II引起的对去甲肾上腺素收缩反应增强是否与45Ca++内流增加或净摄取增加有关。将兔面动脉段等长安装以测量对去甲肾上腺素的45Ca++内流和净摄取。在存在血管紧张素II（0.1 nM）的情况下，对去甲肾上腺素（3 microM）的收缩反应为对照的149.5 +/- 7.4%。这种反应增强与去甲肾上腺素诱导的45Ca++内流或净摄取的变化无关。血管紧张素II还将在含有乙二醇双（β-氨基乙醚）N，N'-四乙酸（2 mM）的无钙缓冲液中获得的对咖啡因的收缩反应增强至对照的148.0 +/- 4.8%。在这两种情况下，用两种蛋白激酶C抑制剂星形孢菌素（10 nM）或钙磷蛋白C（100 nM）预处理可阻止增强。我们得出结论，血管紧张素II增强去甲肾上腺素诱导的血管张力是在刺激的Ca++内流无变化的情况下发生的。这种增强可能是由于细胞内对Ca++的敏感性增加，可能由蛋白激酶C介导。
