Effects of captopril and propanolol on bradykinin-induced changes in vascular pressures, lymph total protein concentration, and weight in canine forelimbs

Abstract

Sixty-minute local intraarterial infusions of bradykinin (0.8, 5, or 10 μg base/min) produced transient forelimb vasodilation and dose-related increases in lymph flow, lymph total protein concentration, total protein transport, and weight in forelimbs perfused at a controlled flow rate. Mean aortic pressure was not affected by these infusion rates of bradykinin. Following pretreatment with captopril, the local intraarterial infusion of these same doses of bradykinin produced sustained systemic hypotension. The increase in protein efflux and edema formation produced by local infusions of bradykinin following pretreatment with captopril was markedly increased during the infusion of the low dose of bradykinin (0.8 μg base/min, ia), but was attenuated during the local infusion of the larger dose of bradykinin (5 μg base/min, ia). Following pretreatment with both captopril and propranolol, the increase in protein efflux and edema formation produced by this larger dose of bradykinin (5 μg base/min) was greater than that produced by infusions of this dose of bradykinin alone or after pretreatment with captopril. Moreover, the increase in protein efflux and edema formation was greater during the infusion of the higher dose of bradykinin than during the infusion of the low dose of this autacoid under these conditions. The 60-min infusion of a massive dose of bradykinin into the left ventricular chamber (280 μg base/min) produced sustained decreases in aortic and forelimb perfusion pressure, but little edema formation relative to that produced by local intraarterial infusions of this agent. In contrast, the 60-min intravenous infusion of only 5 μg base/min of bradykinin following pretreatment with both captopril and propranolol produced profound systemic hypotension and marked increases in protein efflux and edema formation in forelimbs perfused at a controlled flow rate comparable to that produced by the local intraarterial infusion of this dose of bradykinin alone. These data demonstrate that endogenous kininases and catecholamines may dramatically affect the increase in protein efflux and edema formation produced by either local or systemic infusions of bradykinin by modulating the magnitude of the increase in macromolecular permeability.