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 glomerular filtration rate were determined by the clearance of para-aminohippuric acid and inulin, respectively. Each animal acted as its own control. In eight newborn rabbits, a bolus injection of 5 nmol.kg-1 of endothelin-1 caused an initial fall in mean arterial blood pressure followed by a gradual, significant increase in mean arterial blood pressure that lasted for 45 min. The dramatic increase in renal vascular resistance (+28 +/- 4%) induced by endothelin led to a fall in glomerular filtration rate (-12 +/- 4%) and renal blood flow (-16 +/- 3%). In spite of the reduction of glomerular filtration rate and renal blood flow, urine flow and sodium excretion rates increased significantly (+20 +/- 5% and +49 +/- 9%, respectively). In eight additional newborn rabbits, a bolus injection of 1 nmol.kg-1 of endothelin--a dose that usually induces marked renal and systemic vasoconstriction in adult models--did not affect systemic or renal hemodynamics. In conclusion, endothelin induces renal and systemic vasoconstriction and affects water and sodium 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 immaturity and/or interference of high levels of counteracting hormones present during the neonatal period.