Effect of D-600 on inhibition of in vitro renin release in the rat by high extracellular potassium and angiotensin II.

1. Renin was secreted by rat renal cortical slices incubated at 37 degrees C in a physiological saline solution. 2. Secretion was nearly abolished by incubation in a medium containing 60 mM-K. Secretion could be restored to the control level by the addition of 5 X 10(-7) M-D-600 (methoxy verapamil) to 60 mM-K medium. 3. Angiotensin II inhibited renin secretion in a concentration-dependent manner. Concentrations of D-600 ranging from 1 to 3 X 10(-6) M (two to sixfold higher than required to block the inhibitory effect of high K) failed to antagonize the inhibitory effect of angiotensin II. 4. Ca is required for the inhibitory effect of angiotensin II, however, as Ca-depletion (incubation of slices in a medium with Na2EGTA and no added CaCl2)( progressively decreased and finally abolished any inhibitory effect. 5. These results confirm and extend previous observations suggesting that Ca plays an inhibitory coupling role in the control of renin secretion from the juxtaglomerular apparatus. Moreover, they suggest that although voltage-sensitive channels exist on juxtaglomerular cells, angiotensin II activates an independent pathway for Ca mobilization.