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(Circulation. 1996;94:316-322.)
© 1996 American Heart Association, Inc.

Articles

Endothelin and Calcium Antagonists in the Skin Microcirculation of Patients With Coronary Artery Disease

Rene R. Wenzel, MD; Nadine Duthiers, BSc; Georg Noll, MD; Julia Bucher, BSc; Urs Kaufmann, MD; Thomas F. Luscher, MD

Cardiology and Cardiovascular Research, University Hospital, Inselspital, Bern, Switzerland.

Correspondence to Thomas F. Luscher, MD, Professor of Medicine, Cardiology and Cardiovascular Research, University Hospital, Inselspital, CH-3010, Bern, Switzerland.

Background Endothelin, a potent endothelium-derived vasoconstrictor peptide, is elevated in coronary artery disease (CAD); however, its pathophysiological role is uncertain. Calcium antagonists are widely used in patients with CAD. Using laser Doppler flowmetry, we investigated the influence of two endothelin antagonists and the calcium antagonist diltiazem on endogenous and exogenous endothelin in the skin microcirculation of CAD patients and healthy control subjects.

Methods and Results Both endothelin antagonists and diltiazem applied intradermally induced vasodilation in CAD patients, which was more pronounced with the ET_A/ET_B antagonist than with the ET_A antagonist or diltiazem. Exogenous endothelin led to profound vasoconstriction in CAD patients and healthy volunteers. Both endothelin antagonists and diltiazem blunted the vasoconstriction to exogenous endothelin in CAD patients and young healthy volunteers and less so in old healthy volunteers. However, compared with both endothelin antagonists, a 10-times-higher dose of diltiazem was required. Systemic diltiazem (240 mg, slow release) attenuated endothelin-induced vasoconstriction in CAD patients. Neurogenic vasodilation to exogenous endothelin was inhibited by both endothelin antagonists.

Conclusions This study demonstrates that endogenous endothelin of CAD patients contributes to the regulation of vascular tone in the skin microcirculation not only through ET_A receptors but also possibly through ET_B receptors. Diltiazem inhibited endothelin-induced vasoconstriction, but endothelin antagonists were slightly more effective. Thus, endothelin antagonists represent potent new tools to interfere with the vascular effects of endothelin in CAD patients. Future studies must confirm these findings in other areas of the circulation.

Key Words: coronary disease • endothelin • lasers • microcirculation • diltiazem

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