Abstract
Endothelin is a potent vasoconstrictor peptide produced by vascular endothelial cells which could play a role in the physiological regulation of the renal microcirculation. To test this hypothesis, experiments were performed in 24 anaesthetized and mechanically-ventilated newborn rabbits. In 8 newborn rabbits (group 1), a bolus injection of 5 nmol/kg endothelin caused a marked increase in mean blood pressure (MBP) and renal vascular resistance (RVR), leading to a significant fall in glomerular filtration rate (GFR) (by 12% +/- 4%) and renal blood flow (RBF) by 16% +/- 3%). A second group of animals (n = 8) was used for testing the in vivo neutralizing activity of an endothelin-1 antiserum. The antiserum was thereafter infused into 8 additional newborn rabbits (group 3) in order to define the role of endogenous endothelin in modulating the function of the immature kidney. The antiserum induced a surprising increase in RVR (by 34% +/- 9%, P < 0.05) associated with a fall in GFR (by 21% +/- 4%, P < 0.05) and RBF (by 25% +/- 4%, P < 0.05), while the filtration fraction and MBP remained unchanged. The occurrence of a vasoconstrictive response to both high-dose endothelin and to its antiserum could be explained by the recent demonstration that high levels of endothelin lead to renal vasoconstriction, while lower levels induce renal vasodilatation. The present results suggest that endogenous endothelin is active at low levels under normal conditions and that this peptide plays a role in the physiological control of renal function, but not MBP.
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