Endothelin-1 produces no renal vasoconstriction in conscious newborn lambs

Experiments were carried out to investigate the effects of endothelin-1 (ET-1) on renal vascular tone during development under physiological conditions in conscious lambs. Renal blood flow (RBF), renal vascular resistance (RVR), mean arterial pressure (MAP), and heart rate (HR) were measured in conscious, chronically instrumented lambs aged approximately 1 week and 6 weeks before and after intra-arterial (i.a.) injection of 0, 100, 200, and 400 ng/kg body weight of ET-1. In addition, plasma levels of ET-1 were measured in 39 sheep aged 5-85 days. In 6-week-old lambs, i.a. injection of ET-1 was associated with a rapid dose-dependent decrease in RBF that resulted from a dose-dependent increase in RVR. In 1-week-old lambs, there was no renal vasoconstriction observed after ET-1 administration, even at the highest dose tested. In response to i.a. injection of ET-1 to 1-week-old and 6-week-old lambs, MAP increased and there was a concomitant decrease in HR; these effects were dose dependent but not age dependent. Plasma levels of ET-1 were 10.7+/-4.2 pg/ml at 5-10 days, and remained constant throughout the first 3 months of life in conscious sheep. We conclude that ET-1 is not a renal vasoconstrictor agent in the immediate newborn period, and that the effects of ET-1 on renal vascular tone appear to be developmentally regulated.