ACE Inhibitor Causes Kinin-Mediated Renal Vasodilatation in Goldblatt Rabbit

Abstract

P24 ACE inhibitors cause an increase in renal blood flow (RBF) by a kinin-mediated mechanism in the sodium-restricted dog with a high renin level. Previous findings of an inconsistent decrease in plasma angiotensin II after ACE inhibition in Goldblatt rabbits, lead to the hypothesis that a similar effect of ACE inhibition occurs in this high renin model. The systemic blood pressure (BP) and renal hemodynamic effects of enalaprilat (10 mg/kg IV) were compared in 2 groups of rabbits anesthetized with sodium pentobarbital. Blood pressure was measured from the carotid artery and right RBF determined by electroflowmetry. All rabbits underwent clipping of the left renal artery on the average 24 days prior to the acute experiment. Group 1 (n=7) was administered enalaprilat to elicit the normal response to ACE inhibition. Group 2 (n=5) was given the kinin B2 receptor antagonist icatibant as an IV infusion (5 μg/kg/min) during the administration of enalaprilat. This dose of icatibant blocked completely the depressor response to kallidin and itself had no effect on BP or RBF. Results of these experiments are summarized in the Table. Enalaprilat caused a marked rise in RBF and decrease in BP and renal vascular resistance in Group 1. No significant effect of enalaprilat was seen in Group 2. Thus, based on these results, it is concluded that the kallikrein-kinin system plays a major role in the BP and renal hemodynamic response of ACE inhibition in this high renin state.