ROLE OF ENDOGENOUS ENDOTHELIN IN RENAL HEMODYNAMICS OF NEWBORN RABBITS

Endothelin is a potent vasoconstrictor peptide produced by vascular en dothelial cells which could play a role in the physiological regulatio n 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) an d renal vascular resistance (RVR), leading to a significant fall in gl omerular filtration rate (GFR) (by 12% +/- 4%) and renal blood flow (R BF) (by 16% +/- 3%). A second group of animals (n = 8) was used for te sting 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 mod ulating the function of the immature kidney. The antiserum induced a s urprising increase in RVR (by 34% +/- 9%, P <0.05) associated with a f all 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 occurren ce 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 leve ls induce renal vasodilatation. The present results suggest that endog enous endothelin is active at low levels under normal conditions and t hat this peptide plays a role in the physiological control of renal fu nction, but not MBP.