Mechanisms of action of various hormones and vasoactive substances on glomerular ultrafiltration in the rat

Abstract

Angiotensin II (AII) and arginine vasopressin are capable of triggering glomerular mesangial cell contraction in vitro. A similar mechanism acting in vivo to reduce glomerular capillary surface area could account for the decline in the ultrafiltration coefficient [K(f)] that occurs in single glomeruli in response to infusion of these substances. Less clear is the mechanism whereby similar declines in K(f) are induced with infusions of dibutyryl cyclic AMP (DBcAMP), parathyroid hormone (PTH), and prostaglandins, because PTH and PGE2, at least, are incapable of eliciting mesangial cell contraction in vitro. To further explore the factors that regulate K(f) in vivo, the authors performed micropuncture experiments in 47 euvolemic Munich-Wistar rats. Infusions of DBcAMP, PTH, prostaglandins I2 and E2 led to lower mean values for plasma flow rate [Q(A)] and K(f) in superficial glomeruli than were found in animals given vehicle alone (control group), whereas average values for glomerular transcapillary hydraulic pressure difference (ΔP) and total renal arteriolar resistance [R(TA)] tended to be higher. These increases in ΔP and R(TA), and decreases in Q(A) and K(f), with DBcAMP, PTH, PGI2 and PGE2 are typical of changes induced by AII. Indeed, when saralasin, a competitive AII antagonist, was infused together with these various vasoactive substances, the effects on ΔP, Q(A), R(TA), and K(f) were largely abolished. Therefore, the actions of DBcAMP, PTH, PGI2, and PGE2 on the glomerular microcirculation appear to depend on an intermediate action of AII. By contrast, although pitressin (ADH) infusion also led to a significant decline in K(f), saralasin administration did not reverse this change, suggesting that the action of ADH on the glomerular microcirculation is independent of a pathway involving AII. Based on these studies, it seems reasonable to propose that AII and ADH are both potentially important regulators of mesangial cell contraction, and thereby, glomerular capillary filtering surface area and K(f).