Tj. Rabelink et al., EFFECTS OF ENDOTHELIN-1 ON RENAL-FUNCTION IN HUMANS - IMPLICATIONS FOR PHYSIOLOGY AND PATHOPHYSIOLOGY, Kidney international, 46(2), 1994, pp. 376-381
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.