title: Hemodynamic and coronary effects of the endothelin antagonist bosentan in patients with coronary artery disease.
abstract: BACKGROUND
  Endothelin is a potent endothelium-derived vasoconstrictor peptide with proliferative properties. Elevated levels of the peptide occur in coronary artery disease; however, its pathophysiological role as a regulator of coronary tone and structure is uncertain. Endothelin-receptor antagonists are specific tools to clarify this issue and might be useful in the treatment of coronary artery disease.
  
  
  RESULTS
  In a double-blind, placebo-controlled randomized study, we investigated the effects of the ETA/ETB endothelin-receptor antagonist bosentan or placebo on systemic and coronary hemodynamics in 28 patients with angiographically documented stable coronary artery disease by quantitative coronary angiography and an intracoronary Doppler guidewire. Bosentan 200 mg IV decreased systolic blood pressure (P<0. 05), whereas heart rate increased slightly (P<0.05). Coronary diameter increased, particularly in vessels with no or mild angiographic changes (P<0.01). Glycerol trinitrate did not further dilate these segments, whereas coronary diameter increased significantly after nitrate in the placebo group. The increase in coronary diameter after bosentan correlated inversely with plasma LDL-cholesterol levels (P<0.01) in both stenotic and angiographically normal coronary segments. Coronary flow velocity did not change. Bosentan was well tolerated.
  
  
  CONCLUSIONS
  Endogenous endothelin exerts a vasoconstrictor tone in epicardial coronary arteries of patients with coronary artery disease, as evidenced by the vasodilation exerted by the combined ETA/ETB endothelin-receptor antagonist bosentan under acute conditions. Bosentan can safely be given to these patients. Hence, further long-term studies are necessary to determine the therapeutic potential of endothelin-receptor antagonists in patients with coronary artery disease.
authors.affiliation: Cardiology Cardiovascular Research and Hypertension Division, University Hospital, Bern, Switzerland.
authors.forename: R R
authors.initials: RR
authors.lastname: Wenzel
authors.forename: M
authors.initials: M
authors.lastname: Fleisch
authors.forename: S
authors.initials: S
authors.lastname: Shaw
authors.forename: G
authors.initials: G
authors.lastname: Noll
authors.forename: U
authors.initials: U
authors.lastname: Kaufmann
authors.forename: R
authors.initials: R
authors.lastname: Schmitt
authors.forename: C R
authors.initials: CR
authors.lastname: Jones
authors.forename: M
authors.initials: M
authors.lastname: Clozel
authors.forename: B
authors.initials: B
authors.lastname: Meier
authors.forename: T F
authors.initials: TF
authors.lastname: Lüscher
mesh_terms: D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D000077300:Bosentan; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects; D004311:Double-Blind Method; D016232:Endothelins / Q000037:antagonists & inhibitors* / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D000959:Antihypertensive Agents; D016232:Endothelins; D013449:Sulfonamides; D000077300:Bosentan