DOES ENDOTHELIN-1 MEDIATE THE HYPOXEMIA-INDUCED RENAL DYSFUNCTION IN NEWBORN RABBITS

In the newborn rabbit, acute normocapnic hypoxemia increases the renal vascular resistance, leading to renal hypoperfusion and decreased glo merular filtration rate. Endothelin is a potent vasoconstrictor peptid e, produced by vascular endothelial cells, which could play a role as a mediator of the hypoxemia-induced renal dysfunction. To test this hy pothesis, experiments were performed in 24 anesthetized and mechanical ly ventilated newborn rabbits. Renal blood flow and glomerular filtrat ion rate were determined by the clearance of p-aminohippuric acid and inulin, respectively. Each animal acted as its own control. In 8 newbo rn rabbits (group 1), a bolus injection of 5 nmol . kg(-1) of endothel in caused a marked increase in mean blood pressure and renal. vascular resistance leading to a significant fall in glomerular filtration rat e (-12 +/- 4%) and renal blood flow (-16 +/- 3%). A second group of an imals (n = 8) confirmed the neutralizing activity of the endothelin-l antiserum in vivo. In spite of pretreatment with endothelin-l antiseru m, hypoxemia induced an increase in renal vascular resistance(+40 +/- 18%; p < 0.05) associated with a significant fall in glomerular filtra tion rate (-18 +/- 7%) and renal blood flow (-29 +/- 6%) in 8 newborn rabbits (group 3). The present results suggest that endothelin-l does not mediate the hypoxemia-induced renal changes.