REVERSAL OF RENAL CORTICAL ACTIONS OF ANGIOTENSIN-II BY VERAPAMIL AND MANGANESE

Experiments were performed on 19 euvolemic Munich Wistar rats to examine the role of calcium in the action of angiotensin II (AII) on the glomerular microcirculation. Intravenous infusion of a mildly pressor dose of AII(N = 7 rats) led to a significant rise in mean glomerular capillary hydraulic pressure (P(GC) and significant declines in glomerular plasma flow rate (Q(A)) and the ultrafiltration coefficient (K(f)). Because of these offsetting effects, single nephron GFR (SNGFR) and total kidney GFR failed to change significantly. Both afferent and efferent arteriolar resistances (R(A) and R(E)) increased during AII infusion, on average by approximately 40% and 75%, respectively. Despite continued AII infusion, addition of verapamil led to return of values for P(GC), Q(A), K(f), R(A), and R(E) essentially to pre-AII levels. In 7 other rats, verapamil infusion alone failed to exert significant influences on these indices. Likewise, no significant changes in these measures were observed when this same dose of AII was infused into verapamil-pretreated animals. Moreover, intrarenal arterial injection of a nonpressor dose of AII into 6 other rats also resulted in changes in P(GC), Q(A), K(f), and R(E) similar to those seen during intravenous infusion, and addition of mangenese abolished these effects. Since verapamil and manganese are both known to interfere with excitation-contraction coupling of smooth muscle, perhaps by inhibiting transcellular calcium transport, the present results suggest that the calcium ion may be an important cofactor required for the expression of AII action on the glomerular microcirculation, by affecting mesangial and efferent arteriolar smooth muscle contractility.