Acetylcholine-mediated vasodilation in the forearm circulation of patients with heart failure: indirect evidence for the role of endothelium-derived hyperpolarizing factor☆
Section snippets
Study group
Thirteen men and 1 woman (mean age, 50 ± 12 years [range 32 to 65]) with chronic stable CHF due to nonischemic cardiomyopathy were studied. The mean left ventricular ejection fraction was 22 ± 4%. Nine patients were in New York Heart Association functional class II and 5 patients were in functional class III. Cardiovascular medications, which included diuretics, angiotensin-converting enzyme inhibitors, and digoxin in all patients, were withheld 24 hours before the study. Patients with edema,
Results
Resting forearm blood flows did not differ between patients with CHF and normal subjects before infusion of -NMMA (2.1 ± 0.3 vs 2.8 ± 0.3 ml/min/100 ml) or after infusion of -NMMA (2.1 ± 0.3 vs 2.1 ± 0.3 ml/min/100 ml). -NMMA significantly decreased resting forearm blood flow in normal subjects (p <0.05) but not in patients with CHF.
To achieve a comparable degree of vasodilation in the 2 groups, mean doses of acetylcholine and nitroglycerin administered to patients with CHF were
Discussion
The present study demonstrates that during systemic inhibition of cyclooxygenase with indomethacin, regional inhibition of nitric oxide synthase with -NMMA significantly decreased the vasodilatory response to acetylcholine in normal subjects but not in patients with CHF. The presence of a noncyclooxygenase, non-nitric-oxide relaxing factor indicates that EDHF, rather than nitric oxide, may be the predominant endothelium-derived substance mediating vasodilation in response to acetylcholine in
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This study was supported by an investigatorship award from the American Heart Association, New York City Affiliate, New York, New York; by Grant NHLBI R29 HL51433 from the National Institutes of Health, Bethesda, Maryland; by the National Heart Foundation of Australia Clinical Research Program, and Grant 5 M01RR00645, Division of Research Resources, General Clinical Research Program, National Institutes of Health, Bethesda, Maryland.