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The vascular endothelium plays an important role in the control of vasomotor tone and vascular remodelling by producing and releasing various vasoactive agents. 1-4 Many studies in vivo and in vitro have been performed since the effects of endothelium derived relaxing factor (EDRF) were first demonstrated, and several endothelium dependent vasodilators have been identified. Three of these include nitric oxide, which is synthesised by the action of nitric oxide synthase on L-arginine, prostacyclin, 5 6 a product of cyclooxygenase mediated arachidonic acid metabolism, and endothelium derived hyperpolarising factor (EDHF). 7-10 Nitric oxide is believed to be EDRF, or a closely related compound. 11-13
Bradykinin is a potent vasodilator that acts through endothelial B2 kinin receptors to stimulate the release of endothelium derived nitric oxide, prostacyclin, 14 and EDHF, 7 and has been shown to induce endothelium dependent relaxation of human forearm 15 16 and coronary arteries 17 18 in vivo. However, it is uncertain which endothelium dependent vasoactive agent mediates bradykinin induced human coronary vasodilatation in vivo.
We carried out this study to clarify whether endothelium derived nitric oxide contributes to human epicardial and resistance coronary vasodilatation induced by exogenous bradykinin in vivo. NG -monomethyl-L-arginine (L-NMMA), an analogue of L-arginine that specifically inhibits nitric oxide synthase, 19 was used to inhibit the production of nitric oxide, and its effect on the vasodilator response of the coronary vasculature to bradykinin was studied.
Methods
STUDY POPULATION
We studied 20 patients (16 men and four women; mean (SD) age 56 (9) years, range 32 to 69) undergoing coronary angiography for diagnosis of a chest pain syndrome. Each patient's chest pain was atypical for effort angina. All patients had angiographically normal smooth epicardial coronary arteries, normal left ventricular function (contrast ventriculographic ejection fraction [= or >, slanted] 50%) and normal coronary flow reserve. Patients with a previous history of myocardial infarction, cardiomyopathy, valvar heart disease, or heart failure were excluded. Patients with coronary spastic angina who showed angiographically documented coronary spasm (> 50% luminal narrowing) after intracoronary injection of acetylcholine were also excluded. Four patients had hypertension but no echocardiographic evidence of left ventricular hypertrophy. Hypercholesterolaemia (total serum cholesterol > 240 mg/dl) was present in four patients, but their total serum cholesterol values were not above 270 mg/dl...