In vivo effects of endothelin on the renal microcirculation

Endothelin-1 (ET) is a recently discovered vasoconstrictor peptide which is released by renal vascular endothelial cells in response to a number of pathologic insults including ischemia, endotoxemia, bacteremia, and cyclosporine nephrotoxicity. Because microvascular vasoconstriction is an integral component of the acute renal dysfunction associated with these conditions, this study was undertaken to determine the in vivo effects of ET on the renal microcirculation. We used the split hydronephrotic kidney model in decerebrate Sprague-Dawley rats to study vessel diameter and red cell velocity responses to ET using intravital videomicroscopy and doppler velocimetry. Topical administration of increasing concentrations of ET caused a dose-dependent constriction of interlobular arteries which reached a maximum of 27 +/- 5% at an ET concentration of 10(-8) M. A corresponding decrease of 64 +/- 8% in interlobular arterial blood flow was observed. Afferent and efferent arteriole diameters were reduced by 39 +/- 2% and 27 +/- 5%, respectively. These vascular effects were completely prevented by the systemic preinfusion of anti-endothelin antiserum. Infusion of antiserum alone had no effect on systemic hemodynamics or renal microvascular variables, suggesting that ET has little or no role in maintaining basal vascular tone in the kidney. We conclude that ET is a potent in vivo constrictor of the renal microcirculation and may be involved in mediating pathologic vasoconstriction.