Complementary effects of adenosine and angiotensin II in hypoxemia-induced renal dysfunction in the rabbit.
The acute renal effects of hypoxemia and the ability of the co-administration of an angiotensin converting enzyme inhibitor (perindoprilat) and an adenosine receptor antagonist (theophylline) to prevent these effects were assessed in anesthetized and mechanically-ventilated rabbits. Renal blood flow (RBF) and glomerular filtration rate (GFR) were determined by the clearances of para-aminohippuric acid and inulin, respectively. Each animal acted as its own control. In 8 untreated rabbits, hypoxemia induced a significant drop in mean blood pressure (-12 +/- 2%), GFR (-16 +/- 3%) and RBF (-12 +/- 3%) with a concomitant increase in renal vascular resistance (RVR) (+ 18 +/- 5%), without changes in filtration fraction (FF) (-4 +/- 2%). These results suggest the occurrence of both pre- and postglomerular vasoconstriction during the hypoxemic stress. In 7 rabbits pretreated with intravenous perindoprilat (20 microg/kg), the hypoxemia-induced changes in RBF and RVR were prevented. FF decreased significantly (-18 +/- 2%), while the drop in GFR was partially blunted. These results could be explained by the inhibition of the angiotensin-mediated efferent vasoconstriction by perindoprilat. In 7 additional rabbits, co-administration of perindoprilat and theophylline (1 mg/kg) completely prevented the hypoxemia-induced changes in RBF (+ 11 +/- 3%) and GFR (+ 2 +/- 3%), while RVR decreased significantly (-14 +/- 3%). Since adenosine and angiotensin II were both shown to participate, at least in part, in the renal changes induced by hypoxemia, the beneficial effects of perindoprilat and theophylline in this model could be mediated by complementary actions of angiotensin II and adenosine on the renal vasculature.
Prévot
Anne
A
Service de Pédiatrie, Unité de Néphrologie Pédiatrique, Centre Hospitalier Universitaire Vaudois, BH 11, CH-1011 Lausanne, Switzerland.
Huet
Frédéric
F
Semama
Denis S
DS
Gouyon
Jean-Bernard
JB
Guignard
Jean-Pierre
JP
D000241:Adenosine / Q000627:therapeutic use*; D000804:Angiotensin II / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001784:Blood Gas Analysis; D000860:Hypoxia / Q000150:complications*; D007211:Indoles / Q000494:pharmacology; D007444:Inulin / Q000097:blood; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology*; D007677:Kidney Function Tests; D008297:Male; D011817:Rabbits; D012079:Renal Circulation / Q000187:drug effects; D013806:Theophylline / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; C053500:perindoprilat; D007444:Inulin; D013806:Theophylline; D000241:Adenosine