Diminished endothelium-derived relaxing factor activity in an experimental model of chronic heart failure.

Abstract

Abnormalities in vasomotor tone, including enhanced vasoconstriction at rest and diminished vasodilation in response to various stimuli, develop as a consequence of chronic heart failure. This study was undertaken to evaluate whether a specific local mechanism, namely endothelium-derived relaxing factor (EDRF) activity, might be impaired in an experimental model of chronic heart failure. Segments of thoracic aorta (TA) and pulmonary artery (PA) were isolated from a group of rats that had hemodynamic evidence of heart failure 10 weeks after ligation of the left coronary artery (n = 25) and from a group of sham-operated control rats (n = 18). Both endothelium-dependent and endothelium-independent vascular responses were assessed by exposing arterial segments to increasing concentrations of agonists. All studies were performed in the presence of 10 microM indomethacin to avoid the influence of vasoactive prostanoids. The dose-response curve for EDRF-mediated relaxation to acetylcholine was shifted rightward in rats with heart failure, and the concentrations of acetylcholine required to achieve 50% maximal relaxation (EC50) were increased compared with those of control rats in both TA and PA segments. Additionally, the dose-response curve for relaxation to ADP was shifted rightward with significantly increased EC50 in PA segments from rats with heart failure. In contrast, EDRF-mediated relaxation to the calcium ionophore A23187 was similar in the groups. Endothelium-independent relaxation to nitroglycerin was slightly increased in TA but not PA segments in the heart-failure group. Basal EDRF activity, as assessed by the increase in force after exposure to hemoglobin, was diminished in PA segments from rats with heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: M Ontkean, R Gay, B Greenberg
• Journal: Circulation research (Circ Res) Vol. 69 Issue 4 Pg. 1088-96 (Oct 1991) ISSN: 0009-7330 [Print] United States
• PMID: 1934337 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Nitric Oxide
• Calcimycin
• Adenosine Diphosphate
• Acetylcholine

Topics

• Acetylcholine (pharmacology)
• Adenosine Diphosphate (pharmacology)
• Animals
• Aorta, Thoracic (drug effects, metabolism)
• Calcimycin (pharmacology)
• Cardiac Output, Low (metabolism)
• Chronic Disease
• Heart (physiopathology)
• Hemodynamics
• Male
• Nitric Oxide (metabolism)
• Pulmonary Artery (drug effects, metabolism)
• Rats
• Rats, Inbred Strains
• Vasodilation