Effects of endothelin-1 on renal function in humans: Implications for physiology and Pathophysiology

• Published in: Kidney international Vol. 46; no. 2; pp. 376 - 381
• Main Authors: Rabelink, Ton J., Kaasjager, Karin A.H., Boer, Peter, Stroes, Erik G., Braam, Branko, Koomans, Hein A.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 01.08.1994; Nature Publishing
• Subjects: Adult; Biological and medical sciences; Blood Pressure; Endothelins - administration & dosage; Endothelins - pharmacology; Female; Humans; Infusions, Intravenous; Kidney - drug effects; Kidney - physiology; Kidney - physiopathology; Male; Medical sciences; Nifedipine - administration & dosage; Nifedipine - pharmacology; Pharmacology. Drug treatments; Renal Circulation - drug effects; Renal Circulation - physiology; Sodium - urine; Urinary system; Vascular Resistance - drug effects; Vascular Resistance - physiology; Vasoconstriction - drug effects; Vasoconstriction - physiology; Water-Electrolyte Balance - drug effects; Water-Electrolyte Balance - physiology; Human; In vivo; Renal function; Calcium antagonist; Peptide hormone; Vasoconstrictor agent; Endothelin 1; Hemodynamics; Biological activity; Renin angiotensin aldosterone system
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1038/ki.1994.284

Effects of endothelin-1 on renal function in humans: Implications for physiology and pathophysiology. Elevated levels of the vasocontrictor peptide endothelin-1 have been demonstrated in various pathological conditions that are characterized by sodium retention and/or renal vasoconstriction, such as heart failure, hepatorenal syndrome, renal failure and during administration of cyclosporin and radiocontrast. In the present study we studied in seven healthy subjects the renal and endocrine effects of systemic administration of endothelin-1 (0.5, 1.0 and 2.5 ng/kg/min). During endothelin-1 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 low dosages of endothelin-1, that result in a twofold increase in plasma levels, decreased sodium excretion by 36%, without a significant effect on systemic and renal hemodynamics. Infusion of 2.5 ng/kg/min of endothelin-1 further enhanced sodium retention and, in addition, increased renal vascular resistance by 37%. Blood pressure did not change significantly. Pretreatment with the calcium channel blocker nifedipine caused renal vasodilation, which compensated for the renal vasocontriction by endothelin-1 and prevented sodium retention. Apparently, endothelin-1 participates in volume homeostasis in humans, whereas pathophysiologiocal concentrations can contribute to renal vasoconstriction and sodium retention. Calcium channel blockers may protect against these effects of endothelin-1.