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 (PGC) and significant decines in glomerular plasma flow rate (QA) and the ultrafiltration coefficient (Kf). Because of these offsetting effects, single nephron GFR (SNGFR) and total kidney GFR failed to change significantly. Both afferent and efferent arteriolar resistances (RA and RE) 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 PGC, QA, Kf, RA, and RE 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 PGC, QA, Kf, and RE 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.
D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002200:Capillary Resistance / Q000187:drug effects; D005919:Glomerular Filtration Rate; D007672:Kidney Cortex / Q000098:blood supply*; D007678:Kidney Glomerulus / Q000098:blood supply; D008297:Male; D008345:Manganese / Q000494:pharmacology*; D008833:Microcirculation; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D014700:Verapamil / Q000494:pharmacology*
D000804:Angiotensin II; D008345:Manganese; D014700:Verapamil; D002118:Calcium