Reversal of renal cortical actions of angiotensin II by verapamil and manganese.

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 manganese 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. Reversion par le verapamil et le manganese des actions de l'angiotensine II sur le cortex renal. Des experiences ont ete realisees sur 19 rats Munich Wistar euvolemiques afin d'etudier le role du calcium dans l'action de l'angiotensine II sur la microcirculation glomerulaire. La perfusion intraveineuse d'une dose moderement pressive d'AII (N = 7 rats) determine une augmentation significative de la pression hydraulique capillaire glomerulaire moyenne (P GC ) et des diminutions significatives du debit plasmatique glomerulaire (Q A ) et du coefficient d'ultrafiltration (K f ). Du fait de l'annulation reciproque de ces effets les debits de filtration individuels (SNGFR) et globaux (GFR) ne changent pas significative ment. Les resistances arteriolaires afferente et efferente (R A et R E ) augmentent au cours de la perfusion d'AII, en moyenne de 40% et 75%, respectivement. Malgre la poursuite de la perfusion d'AII l'administration de verapamil determine un retour aux valeurs initiales de P GC , Q A , K f , R A , et R E . Chez 7 autres rats la perfusion de verapamil seul n'influence pas significativement ces variables. Il n'est pas observe non plus de modification significative des ces variables quand la meme dose d'AII est administree a des animaux pre-traites par le verapamil. De plus, l'injection dans l'artere renale d'une dose non pressive d'AII chez 6 autres rats determine aussi des modifications de P GC Q A , K f , et R E semblables a celles observees au cours de l'injection intraveineuse et l'addition de manganese abolit encore ces effets. Du fait que le verapamil et le manganese sont tous deux connus pour interferer avec le couplage excitation-contraction du muscle lisse, probablement par l'inhibition du transport de calcium transcellulaire, les resultats suggerent que l'ion calcium peut etre un co-facteur important necessaire a l'expression de l'action de AII sur la microcirculation glomerulaire en affectant la contractilite du muscle lisse mesangial et arteriolaire efferent.