Relation between inhibition of renal angiotensin II production and hemodynamic effect of captopril in anesthetized rabbit

Abstract

This study was conducted in order to determine the relation between the renal hemodynamic effect of an angiotensin converting enzyme (ACE) inhibitor and its effect upon plasma angiotensin II levels in the rabbit. The effect of captopril upon arterial and renal venous plasma angiotensin II concentrations was assumed to reflect the systemic and renal actions of ACE inhibition. Systemic blood pressure, renal blood flow (RBF), and arterial and renal venous plasma concentrations of angiotensin II and angiotensin I were measured in five groups of anesthetized rabbits; groups Ia and Ib consisted of sodium-replete and group II sodium-deplete rabbits in which captopril was administered in a maximal ACE inhibiting dose of 2 mg/kg, intravenously, followed by an intra-arterial (group Ia) or an intravenous (group Ib) infusion of 1 mg/kg per h; group III consisted of sodium-replete rabbits given a low captopril dose of 10 micrograms/kg per min, intra-arterially; and group IV represented control levels. In a separate group of rabbits (group V) the effects of a low dose of 10 micrograms/kg per min captopril in the presence of the angiotensin II antagonist DuP 753 were studied. The high dose of captopril decreased blood pressure and increased RBF in both sodium-replete and sodium-deplete rabbits. Arterial and renal venous angiotensin II levels were low in group Ia compared with groups Ib and II; however, in all three groups angiotensin II levels were markedly decreased during high-dose captopril administration. The low dose of captopril caused approximately the same increase in RBF, despite no change in angiotensin II levels. Angiotensin I concentrations tended to increase during high-dose captopril administration due to blockade of negative feedback of renin release. A time trend did not account for the results, since blood pressure, RBF and angiotensin II were stable over a 1-h period in control experiments. These results suggest that different pools of renal angiotensin II may exist, and that a small critically located pool, possibly in the endothelium, may be important in renal vascular control.