Effect of Endothelin-1 on Exercise-Induced Vasodilation in Normal Subjects and in Patients With Heart Failure

Endothelin-1 is an endothelium-derived 21-amino acid peptide that mediates vasoconstriction through stimulation of specific cell surface receptors on vascular smooth muscle cells.[ 1 Masaki T Kimura S Yanagisawa M Goto K Molecular and cellular mechanism of endothelin regulation Implications for vascular function. Circulation. 1991; 84: 1457-1468 Crossref PubMed Scopus (409) Google Scholar ]The pathophysiologic role of endothelin-1 in the regulation of skeletal muscle blood flow during exercise in heart failure has not been fully characterized. Plasma concentrations of endothelin-1 are increased at rest and during maximal exercise in patients with congestive heart failure when compared with those in normal subjects and are inversely correlated with maximal exercise capacity.[ 2 Cody RJ Haas GJ Binkley PF Capers Q Kelley R Plasma endothelin correlates with the extent of pulmonary hypertension in patients with chronic congestive heart failure. Circulation. 1992; 85: 504-509 Crossref PubMed Scopus (605) Google Scholar , 3 Krum H Goldsmith R Wilshire-Clement M Miller M Packer M Role of endothelin in the exercise intolerance of chronic heart failure. Am J Cardiol. 1995; 75: 1282-1283 Abstract Full Text PDF PubMed Scopus (87) Google Scholar ]However, in dogs with heart failure induced by rapid ventricular pacing, increased plasma concentrations of endothelin-1 are associated with attenuation of the vasoconstricting effects of exogenous endothelin-1 when compared with control animals.[ 4 Cavero PG Miller WL Heublein DM Margulies KB Burnett JCJ Endothelin in experimental congestive heart failure in the anesthetized dog. Am J Physiol. 1990; 259: F312-F317 PubMed Google Scholar ]The current study was undertaken to determine the effects of administration of endothelin-1 in the brachial artery on forearm blood flow at rest and during rhythmic handgrip exercise in normal subjects and patients with chronic heart failure.