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.