Endothelin-1 produces no renal vasoconstriction in conscious newborn lambs

Abstract

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.

Nitric oxide modulates renal vasoconstrictor effect of endothelin-1 in conscious lambs

“…It was concluded that ET-1 is a renal vasodilator in the near-term fetal sheep, resulting from activation of ET B receptors presumably through production of NO. Our previous studies in conscious newborn lambs have also shown that ET-1 administration elicits no renal vasoconstriction [6]. In fact, a renal vasodilation is seen-albeit transiently-after ET-1 injection in 1-weekold lambs (see also Fig.…”

“…Measurements were continued for 5 min before and 20 min after close arterial injection of 100 ng/kg of ET-1. The dose of ET-1 was selected from previous dose-response studies [6] as the EC 50 RBF response to ET-1. The dose of l-NAME was selected from previous dose-response studies [13,15] as that required to inhibit intrarenal arterial NO production for a minimum of 60 min in conscious lambs aged 1-6 weeks of postnatal life.…”

“…Previously, we measured the acute dose-dependent effects of ET-1 on renal haemodynamics in conscious, chronically instrumented lambs in vivo [6]. There was a dose-dependent increase in renal vascular resistance (RVR) that resulted in a decrease in renal blood flow (RBF) in conscious lambs aged~6 weeks of postnatal life.…”

Haemodynamic responses to angiotensin II in conscious lambs: role of nitric oxide and prostaglandins

“…Surgery was performed using aseptic techniques, as previously described [29,37]. Briefly, anaesthesia was induced with a mask and isoflurane (∼5%) in oxygen, the trachea was intubated and anaesthesia was maintained by ventilating the lungs with isoflurane (1.5-2.5%) in a 3:2 mixture of nitrous oxide and oxygen.…”