Hypercholesterolemia does not impair endothelium-derived relaxing factor-mediated venodilation, with maximal relaxation to bradykinin of 103% vs 80% in controls (P=0.08).
Observational (n=25)
Does hypercholesterolemia impair endothelium-dependent vasodilation in human veins in vivo?
Hypercholesterolemia does not impair endothelium-derived relaxing factor-mediated venodilation in humans, suggesting that arterial endothelial dysfunction in hypercholesterolemia may require factors beyond just elevated lipoproteins interacting with the endothelium.
Absolute Event Rate: 103% vs 80%
p-value: p=0.08
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: Full 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 alpha-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 micrograms/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 ED50 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.
Bedarida et al. (Wed,) conducted a observational in Hypercholesterolemia (n=25). Hypercholesterolemia vs. Normocholesterolemia was evaluated on Maximal relaxation induced by bradykinin (p=0.08). Hypercholesterolemia does not impair endothelium-derived relaxing factor-mediated venodilation, with maximal relaxation to bradykinin of 103% vs 80% in controls (P=0.08).