Role of endothelin in spontaneous phasic contraction of human coronary arteries.
Isolated human coronary arteries are known to develop spontaneous phasic contractions (SPCs). The goal of the present study was to assess the role of endothelin (ET) in these contractions. Endothelium-denuded rings from left anterior descending (LAD) coronary arteries of patients with coronary artery disease (CAD; n = 3) undergoing cardiac transplantation developed SPCs within 1-2 h. The contractions were abolished by the ETA receptor antagonist BQ-123 or the mixed ET receptor antagonist bosentan (1 and 3 microM), whereas the contractions persisted for several hours in control rings. Exogenous ET-1 (10 pM) increased the amplitude of SPCs and initiated SPCs in rings that did not exhibit SPCs. Higher concentrations of ET-1 (> or = 1 nM) were able to re-induce SPC in rings in which SPCs had been abolished by BQ-123 or bosentan. These results suggest that ET plays an important role in spontaneous phasic contractions of isolated human coronary artery rings.
Dagassan
P H
PH
Pharma Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Clozel
M
M
Breu
V
V
Clozel
J P
JP
D003331:Coronary Vessels / Q000502:physiology*; D016232:Endothelins / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000502:physiology; D014661:Vasoconstriction
D016232:Endothelins; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; C072247:cyclo(Trp-Asp-Pro-Val-Leu)