Prevention of hypoxemia-induced renal dysfunction by perindoprilat in the rabbit

Abstract

The role of angiotensin II, a potent postglomerular vasoconstrictor, in the hypoxemiainduced renal changes is still controversial. The ability of perindoprilat, an angiotensin converting-enzyme inhibitor, to prevent the acute renal effects of hypoxemia was assessed in 22 anesthetized-ventilated rabbits. In 8 untreated rabbits, hypoxemia induced a significant drop in mean blood pressure (MBP) (−12 ± 2%), glomerular filtration rate (GFR) (−16 ± 3%) and renal blood flow (RBF) (−12 ± 3%) with a concomittant increase in renal vascular resistance (RVR) (+18 ± 5%) and urine flow rate (+33 ± 14%), and without any changes in filtration fraction (FF) (−4 ± 2%). This suggests the occurrence of glomerular vasoconstriction during the hypoxemic stress. In 7 normoxemic rabbits, intravenous perindoprilat (20 μg kg ) induced an increase in urine flow rate (+17 ± 4%) and RBF (+17 ± 4%), and a decrease in MBP (−6 ± 1%), RVR (−14 ± 3%) and FF (−11 ± 2%) without a significant change in GFR. The drop in FF and the increase in RBF suggests preferential postglomerular vasodilatation. In 7 rabbits, perindoprilat prevented the occurence of the hypoxemia-induced changes in RBF and RVR without improving MBP. FF decreased significantly (−18 ± 2%), while the drop in GFR (−7 ± 2%) was partially blunted and the increase in urine flow rate (+25 ± 9%) was confirmed. These results could be explained by the inhibition of the angiotensin-mediated efferent vasoconstriction and by the inhibition of bradykinin degradation by perindoprilat. These data confirm the ability of converting-enzyme inhibitors to prevent the renal hypoperfusion induced by acute hypoxemia.