Endothelin-mediated cardiorenal hemodynamic and neuroendocrine effectsare attenuated by nitroglycerin in vivo

Wayne L. Miller, Patricia G. Cavero, Larry L. Aarhus, Denise M. Heublein, John G. Burnett

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12 Scopus citations

Abstract

Endothelin-l may function pathophysiologically as a counterregulatory vasoconstrictor peptide that ismodified in its activity by the opposing action ofendothelium-derived relaxing factor(s) (EDRF). Thepresent study determined in part the integratedcardiorenal and endocrine actions of pathophysiologic plasma concentrations of endothelin in theanesthetized dog. In addition, nitroglycerin, whichinhibits vascular smooth muscle contraction by increasing cGMP in a mechanism similar to EDRF, acts like an endogenous nitrovasodilator. Therefore, we tested the hypothesis that nitroglycerinwould effectively antagonize the cardiac and renalactions of exogenous endothelin. The results confirm that endothelin-l-mediated vasoconstriction invivo is heterogenous with a greater renal than coronary action. Further, nitroglycerin effectivelyblocked endothelin-l-mediated coronary flow reductions, but only partially antagonized reductionsin renal blood flow. Endothelin-l-induced reduction in cardiac output also was not antagonized by nitroglycerin despite its effects to preserve coronary blood flow. Nitroglycerin did, however, antagonize endothelin-induced elevations in plasma epinephrine, norepinephrine, and aldosterone. Theseresults would suggest that in pathophysiologicstates where endothelin-l is elevated, such as hypertension or congestive heart failure, there is amajor compromising of renal function, and also theproduction of cardiac ischemia. Since exogenous nitroglycerin is relatively ineffective in antagonizingthe renal vasoconstrictive effects of endothelin, itmay be that the endogenous vasodilating systems, such as ERDF and prostacyclin, are inadequate insuch pathologic states to counter the vasoconstrictoreffects of endothelin. Am J Hypertens 1993;6:156-163.

Original languageEnglish (US)
Pages (from-to)156-163
Number of pages8
JournalAmerican journal of hypertension
Volume6
Issue number2
DOIs
StatePublished - Feb 1993

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Keywords

  • Cardiorenal hemodynamics
  • Dog
  • Endothelin-l
  • Nitroglycerin

ASJC Scopus subject areas

  • Internal Medicine

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