Prevention of hypoxemia-induced renal dysfunction by perindoprilat in the rabbit.
The role of angiotensin II, a potent postglomerular vasoconstrictor, in the hypoxemia-induced 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 microg/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.
Huet
F
F
Service de Pédiatrie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Gouyon
J B
JB
Guignard
J P
JP
D000804:Angiotensin II / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D005919:Glomerular Filtration Rate / Q000187:drug effects; D000860:Hypoxia / Q000150:complications*; D007211:Indoles / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000209:etiology / Q000517:prevention & control*; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D011817:Rabbits; D012079:Renal Circulation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D000804:Angiotensin II; D002245:Carbon Dioxide; C053500:perindoprilat; D010100:Oxygen