EFFECTS OF ENDOTHELIN ON RENAL-FUNCTION IN NEWBORN RABBITS

The renal effects of endothelin-1 were investigated in 16 anesthetized and mechanically ventilated newborn rabbits. Renal blood flow and glo merular filtration rate were determined by the clearance of para-amino hippuric acid and inulin, respectively. Each animal acted as its own c ontrol. In eight newborn rabbits, a bolus injection of 5 nmol.kg-1 of endothelin-1 caused an initial fall in mean arterial blood pressure fo llowed by a gradual, significant increase in mean arterial blood press ure that lasted for 45 min. The dramatic increase in renal vascular re sistance (+28 +/- 4%) induced by endothelin led to a fall in glomerula r filtration rate (-12 +/- 4%) and renal blood flow (-16 +/- 3%). In s pite of the reduction of glomerular filtration rate and renal blood fl ow, urine flow and sodium excretion rates increased significantly (+20 +/- 5% and +49 +/-9%, respectively). In eight additional newborn rabb its, a bolus injection of 1 nmol.kg-1 of endothelin-a dose that usuall y induces marked renal and systemic vasoconstriction in adult models-d id not affect systemic or renal hemodynamics. In conclusion, endotheli n induces renal and systemic vasoconstriction and affects water and so dium homeostasis during the neonatal period. These effects occur under higher doses than those used in adult animals. This age difference in systemic and renal responsiveness is probably mediated by receptor im maturity and/or interference of high levels of counteracting hormones present during the neonatal period.