Endothelin: A potent renal and systemic vasoconstrictor peptide

Endothelin is an endothelial cell-derived peptide recently shown to possess potent vasoconstrictor properties. Bolus intravenous injections of endothelin (5-450 pmol) into anesthetized Munich-Wistar rats induced a marked pressor effect, the magnitude and duration of which were dose dependent. Maximal systemic and renal responses occurred within 20 min and persisted for >90 min in the higher dose range. In response to bolus dosages of 25 pmol or greater, renal plasma flow fell proportionately more than glomerular filtration rate, resulting in an increase in filtration fraction. In micropuncture studies of rats given continuous intravenous infusions of endothelin (0.63 pmol/min), the peptide caused a proportionately greater elevation of efferent than afferent arteriolar resistance, with a marked elevation of glomerular capillary hydraulic pressure and a lower glomerular capillary ultrafiltration coefficient. Endothelin was modestly natriuretic when systemic pressure rose and renal function was not severely impaired. This potent renal and systemic vasoconstrictor may play an important role in glomerular injury and in the pathophysiology of a variety of clinical microvasculopathies.