Chloride channel blockers attenuate the inhibition of renin secretion by angiotensin II

The aim of this study was to assess the relevance of chloride channels to t he inhibitory effect of angiotensin II (ANGII) on renin secretion. We thus examined the effects of the chloride channels blockers IAA-94 and niflumic acid, the Na-K-Cl cotransport blocker bumetanide and substitution of isethi onate for extracellular chloride on the action of ANGII on renin secretion from isolated perfused rat kidneys. Renin secretion prestimulated by isopro terenol (10 nmol/l) was almost completely blocked by ANGII with a concentra tion yielding a half-maximal response (EC50) of around 150 nmol/l. In the p resence of IAA-94 and niflumic acid the EC50 for ANGII was shifted to about 400 nmol/l. In the presence of bumetanide and isethionate renin secretion responded more sensitively to ANGII and the EC50 for ANGII was below 100 nm ol/l. On the assumption that the chloride equilibrium potential in renin-se creting cells is more positive than the membrane potential, our findings wo uld suggest that the inhibitory effect of ANGII is enhanced when chloride e ntry is blocked and attenuated when chloride efflux is impaired. Activation of chloride channels therefore probably contributes to the inhibitory acti on of ANGII on renin secretion.