EFFECTS OF ENDOTHELIN-1 ON RENAL-FUNCTION IN HUMANS - IMPLICATIONS FOR PHYSIOLOGY AND PATHOPHYSIOLOGY

Elevated levels of the vasocontrictor peptide endothelin-l have been d emonstrated in various pathological conditions that are characterized by sodium retention and/or renal vasoconstriction, such as heart failu re, hepatorenal syndrome, renal failure and during administration of c yclosporin and radiocontrast. In the present study we studied in seven healthy subjects the renal and endocrine effects of systemic administ ration of endothelin-1 (0.5, 1.0 and 2.5 ng/kg/min). During endothelin -l infusion plasma levels rose from 3.2 +/- 0.5 to respectively 5.0 +/ - 0.8, 6.2 +/- 0.5 and 8.5 +/- 1.1 pmol/liter, values that can also be observed in physiological and pathological conditions. Infusion of lo w dosages of endothelin-1, that result in a twofold increase in plasma levels, decreased sodium excretion by 36%, without a significant effe ct on systemic and renal hemodynamics. Infusion of 2.5 ng/kg/min of en dothelin-1 further enhanced sodium retention and, in addition, increas ed renal vascular resistance by 37%. Blood pressure did not change sig nificantly. Pretreatment with the calcium channel blocker nifedipine c aused renal vasodilation, which compensated for the renal vasocontrict ion by endothelin-1 and prevented sodium retention. Apparently, endoth elin-1 participates in volume homeostasis in humans, whereas pathophys iologlocal concentrations can contribute to renal vasoconstriction and sodium retention. Calcium channel blockers may protect against these effects of endothelin-1.