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Basal release of nitric oxide is decreased in the coronary circulation in patients with heart failure
M Mohri1, K Egashira, T Tagawa
1Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University, Faculty of Medicine, Higashi-ku, Fukuoka, Japan. mmohri@cardiol.med.kyushu-u.ac.jp
Insights
Basal nitric oxide release in coronary arteries is reduced in heart failure patients. This study investigated nitric oxide synthesis inhibition in coronary arteries of heart failure patients and controls.
Area of Science:
- Cardiovascular Physiology
- Human Physiology
- Vascular Biology
Background:
- Basal release of endothelium-derived nitric oxide (NO) in coronary arteries is crucial for vascular tone.
- Alterations in NO bioavailability are implicated in the pathophysiology of heart failure.
Purpose of the Study:
- To investigate the role of nitric oxide synthesis in regulating basal tone of conduit and resistance coronary arteries in human heart failure.
- To evaluate the effect of inhibiting nitric oxide synthesis on coronary blood flow and diameter in patients with heart failure.
Main Methods:
- Quantitative coronary angiography and Doppler guide wire were used to measure coronary arterial diameter and blood flow velocity.
- Intracoronary administration of N(G)-monomethyl-L-arginine (L-NMMA), a nitric oxide synthesis inhibitor, was performed in patients with heart failure and healthy controls.
- Measurements were taken in awake patients to assess basal coronary vascular tone.
Main Results:
- Inhibition of nitric oxide synthesis with L-NMMA reduced coronary blood flow in both heart failure patients and controls.
- The reduction in coronary blood flow was significantly smaller in heart failure patients compared to controls.
- The blunted vasoconstricting response to L-NMMA in heart failure was inversely correlated with left ventricular contractile function.
Conclusions:
- Basal release of nitric oxide in the coronary circulation is decreased in patients with heart failure.
- Impaired nitric oxide bioavailability contributes to altered coronary vascular tone in heart failure.
- These findings highlight a potential therapeutic target for managing coronary dysfunction in heart failure.
Abstract:
It is unknown whether basal release of endothelium-derived nitric oxide in the coronary artery is altered in heart failure in humans. The aim of the present study was to evaluate the effect of inhibition of nitric oxide synthesis on basal tone of the conduit and resistance coronary arteries in awake patients. Coronary blood flow velocity (Doppler guide wire) and coronary arterial diameter (quantitative coronary angiography) were measured in 14 patients with heart failure caused by nonischemic left ventricular dysfunction (7 idiopathic dilated cardiomyopathy and 7 valvular insufficiency) and 7 patients with normal ventricular function (controls). Intracoronary N(G)-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthesis, at graded doses decreased coronary blood flow in both groups. However, the magnitude of flow reduction was smaller in patients with heart failure than in control patients (P<.0001). The magnitude of coronary blood flow reduction in response to L-NMMA inversely correlated to indexes of left ventricular contractile function (P<.01) but was not affected by the cause of heart failure. Constriction of the large epicardial coronary artery with L-NMMA also tended to be attenuated in patients with heart failure. In summary, vasoconstricting response to L-NMMA was blunted in the coronary resistance artery in heart failure in vivo. These findings suggest that basal release of nitric oxide in the coronary circulation is decreased in patients with heart failure.