RESPONSIVENESS TO BRADYKININ IN VEINS OF HYPERCHOLESTEROLEMIC HUMANS

[摘要] Background. Hypercholesterolemia impairs endothelium-dependent dilation in arteries. We tested the hypothesis that hypercholesterolemia impairs endothelium dependent vasodilation by an interaction between elevated plasma lipoproteins and a presumably normal endothelium using human veins in vivo; veins do not generally develop atherosclerosis and are appropriate for testing functional alterations. Methods and Results. Pull dose-response curves were constructed in 13 hypercholesterolemic and 12 normocholesterolemic subjects by infusing bradykinin (0.25 to 508 ng/min) into hand veins preconstricted with the cu-adrenergic agonist phenylephrine. The maximal relaxation induced by bradykinin was 80+/-38% in the controls and 103+/-40% in subjects with hypercholesterolemia (P=.08). Responsiveness to bradykinin was also determined after infusion of indomethacin (5.4 mu g/min), a cyclooxygenase inhibitor, to block the contribution of prostaglandins; maximal responsiveness was greater in hypercholesterolemic subjects (112+/-41%) than in controls (81+/-31%) (P=.03). Hypercholesterolemic subjects were more sensitive to bradykinin, with an ED,, of 4.2 ng/min versus 10.9 ng/min in controls (P=.05); a similarly increased sensitivity was found in the presence of indomethacin. The response to a maximally effective dose of nitroglycerin was greater in hypercholesterolemic subjects (142+/-31%) versus 106+/-28% in controls (P=.007). In five hypercholesterolemic subjects, treated with lovastatin to normalize serum cholesterol concentrations, maximal responsiveness to bradykinin decreased from 103+/-52% to 80+/-28%. Conclusions. These results demonstrate that hypercholesterolemia in humans does not impair endothelium-derived relaxing factor-mediated venodilation.

[发布日期] 1993-12-01

[关键词] ENDOTHELIUM-DEPENDENT RELAXATION;PORCINE CORONARY-ARTERIES;CHOLESTEROL-FED RABBITS;NITRIC-OXIDE;RELAXING FACTOR;L-ARGININE;EXPERIMENTAL ATHEROSCLEROSIS;VASCULAR REACTIVITY;AORTA;LIPOPROTEINS