Long-term changes in the response of conductance and resistance coronary vessels to endothelium-dependent and independent vasodilators. A double-blind placebo-controlled study of the effect of a 6-month treatment with cilazapril

Ital Heart J. 2000 Oct;1(10):674-83.

Abstract

Background: The aim of this study was to assess the effect of a 6-month treatment with the inhibitor of the angiotensin-converting enzyme cilazapril on the response of conductance and resistance vessels to endothelium-dependent and independent vasodilators, in a randomized placebo-controlled parallel group single center study.

Methods: Quantitative angiographic and Doppler flow time-averaged peak velocity measurements were performed in an artery with < 30% diameter stenosis after sequential selective intracoronary injection of papaverine (7 mg), acetylcholine (0.036, 0.36 and 3.6 microg/ml at 2 ml/min) and isosorbide dinitrate. Repeated assessment was performed after a 6-month treatment with cilazapril 20 mg/day or placebo. Thirty-four patients were enrolled in the study undergoing elective percutaneous coronary interventions for stable angina. Main outcome measures were percent differences from baseline and absolute measurements of mean coronary cross-sectional area, coronary flow time-averaged peak velocity and flow resistance in the initial study and at follow-up for the placebo and the treated group.

Results: No significant differences between the placebo and the treated group were observed in the modifications of cross-sectional area after acetylcholine and isosorbide dinitrate and in the response of time-averaged peak velocity to papaverine. After the maximal concentration of acetylcholine a high but statistically not significant increase in flow and a decrease in flow resistance were observed in the treated group (medians: 45% increase vs 4% increase for coronary flow, and 44% decrease vs 1% increase for flow resistance in the cilazapril and in the treated group, respectively, p = NS).

Conclusions: In patients with coronary artery disease, a 6-month treatment with 20 mg of cilazapril/day did not modify the response to endothelium-independent and dependent vasodilators of epicardial arteries without any significant stenoses but induced a consistent, although not significant, increase in flow and decrease in flow resistance after acetylcholine.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Antihypertensive Agents / therapeutic use*
  • Cilazapril / therapeutic use*
  • Coronary Circulation / drug effects*
  • Coronary Disease / drug therapy*
  • Coronary Disease / physiopathology
  • Double-Blind Method
  • Female
  • Heart Rate / drug effects
  • Humans
  • Isosorbide Dinitrate / pharmacology
  • Male
  • Middle Aged
  • Papaverine / pharmacology
  • Vascular Resistance / drug effects*
  • Vasodilator Agents / pharmacology*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Vasodilator Agents
  • Cilazapril
  • Papaverine
  • Isosorbide Dinitrate
  • Acetylcholine