Contribution of kininase II to the waning of vascular actions of bradykinin

Abstract

The mechanism(s) of the waning of the vasodilation and increase in vascular permeability during prolonged local intraarterial infusions of bradykinin (BK) was investigated in this study. Treatment with phentolamine or saralasin failed to prevent the waning of the vasodilation during the prolonged infusion of BK into forelimbs perfused at constant flow. In contrast, BK produced a sustained vasodilator response after treatment with captopril. Forelimb weight and lymph analysis were used to quantitate edema formation and to determine the duration of the increase in vascular permeability during prolonged local intra-arterial infusions of BK into forelimbs perfused at constant flow. The lymph-to-plasma ratios (L/P) for protein and FITC-Dextrans (fluorescein isothiocyanate dextrans, 70,000 Da) were determined, and clearances for protein and FITC-D were calculated. BK markedly increased fluid filtration, the protein L/P, and protein clearance resulting in edema formation. The protein L/P remained markedly elevated throughout the experimental period. The FITC-D L/P was markedly increased in the groups of animals in which the tracer was injected intravenously at the start or 8 min after the start of the prolonged BK infusion. In the groups of animals in which the tracer was injected intravenously 15-60 min after the start of the prolonged BK infusion, the FITC-D L/P failed to exceed the FITC-D L/P in control animals, although the protein L/P remained elevated. Pretreatment with both captopril and propranolol dramatically potentiated the magnitude of the increase in protein clearance, the filtration rate, and edema formation produced by BK but failed to affect the duration of the transient increase in vascular permeability.