Scriabine A, Anderson C L, Janis R A, Kojima K, Rasmussen H, Lee S, Michal U
J Cardiovasc Pharmacol. 1984;6 Suppl 7:S937-43.
The available evidence indicates that nitrendipine and other dihydropyridines with a similar pharmacological action exert their therapeutic effects by inhibiting Ca2+ channels. In our recent experiments, nitrendipine was shown to block K+-stimulated 45Ca2+ uptake and K+-induced contractions of isolated rabbit aortic rings. Its IC50 were 4.7 and 8.9 nM for inhibition of Ca2+ uptake and of contractions, respectively. There was no statistically significant difference between the two values. At higher concentrations, nitrendipine also reduced norepinephrine-induced 45Ca2+ uptake and norepinephrine-induced contractions of rabbit aortic strips. The norepinephrine-induced contractions were only slightly (21%) reduced by nitrendipine at 10 microM. Nitrendipine at 10 nM and higher concentrations inhibited K+- or angiotensin-II-(AII) induced release of aldosterone from isolated bovine adrenal glomerulosa cells. The drug was more potent and more effective in inhibiting K+- than AII-induced aldosterone release. Dantrolene, 25 microM, enhanced the inhibitory activity of nitrendipine on AII-stimulated aldosterone release. Acute renal failure produced by either glycerol or gentamicin in rats was antagonized by nitrendipine at oral doses of 15-25 mg/kg/day. Our studies confirmed previously reported observations that the usefulness of nitrendipine in the treatment of hypertension may be determined not only by its vasodilator action. We demonstrated that nitrendipine has a direct inhibitory effect on the release of aldosterone from adrenal glomerular cells. In addition to a previously described diuretic action, nitrendipine was shown to have renal cytoprotective activity.
现有证据表明，尼群地平和其他具有类似药理作用的二氢吡啶类药物通过抑制钙通道发挥其治疗作用。在我们最近的实验中，尼群地平被证明可阻断钾离子刺激的45Ca2+摄取以及离体兔主动脉环的钾离子诱导收缩。其抑制钙摄取和收缩的半数抑制浓度（IC50）分别为4.7和8.9 nM。这两个值之间无统计学显著差异。在较高浓度下，尼群地平还可降低去甲肾上腺素诱导的兔主动脉条的45Ca2+摄取和去甲肾上腺素诱导的收缩。在10 microM浓度下，尼群地平仅使去甲肾上腺素诱导的收缩略有降低（21%）。10 nM及更高浓度的尼群地平可抑制钾离子或血管紧张素II（AII）诱导的离体牛肾上腺球状带细胞醛固酮释放。该药物在抑制钾离子诱导的醛固酮释放方面比抑制AII诱导的醛固酮释放更有效且作用更强。25 microM的丹曲林增强了尼群地平对AII刺激的醛固酮释放的抑制活性。大鼠由甘油或庆大霉素引起的急性肾衰竭可被口服剂量为15 - 25 mg/kg/天的尼群地平拮抗。我们的研究证实了先前报道的观察结果，即尼群地平在高血压治疗中的有效性可能不仅取决于其血管舒张作用。我们证明尼群地平对肾上腺球状细胞醛固酮释放有直接抑制作用。除了先前描述的利尿作用外，尼群地平还具有肾细胞保护活性。
