Inhibitory effects of calcium channel agonists on renin release from rat kidney cortical slices.

Inhibitory effects of calcium channel agonists such as Bay K 8644 [methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)- pyridine-5-carboxylate] and CGP 28392 [ethyl-4-(2-difluoromethoxyphenyl)-1,4,5,7-tetrahydro-2-methyl- 5-oxofuro-(3,4-b)-pyridine-3-carboxylate] on renin release were investigated, using rat kidney cortical slices. Bay K 8644 or CGP 28392 alone had no effect on renin release from the slices, whereas both compounds produced a concentration-dependent inhibition of the release in the presence of 15 mM potassium. The Bay K 8644-induced inhibitory action was more effective and potent than that seen with CGP 28392. Bay K 8644 caused a leftward shift of the dose-response curve of the potassium-induced decrease in renin release. In contrast, the dose-response relationships of the release to norepinephrine and methoxamine were not affected by Bay K 8644. The combination of the maximum effective doses of calcium channel agonists and norepinephrine exerted an apparent additive effect on the release of renin. The inhibitory effects of Bay K 8644 and CGP 28392 were attenuated in the presence of decreased extracellular calcium concentrations. Nifedipine and verapamil elicited a blocking action on the inhibition of renin release by Bay K 8644 or CGP 28392, in a concentration-dependent manner. Calmodulin antagonists, such as trifluoperazine and calmidazolium suppressed significantly the decreasing effect of Bay K 8644 or CGP 28392 on renin release from the slices.(ABSTRACT TRUNCATED AT 250 WORDS)