Responsiveness to bradykinin in veins of hypercholesterolemic humans

• Published in: Circulation (New York, N.Y.) Vol. 88; no. 6; pp. 2754 - 2761
• Main Authors: BEDARIDA, G. V, BUSHELL, E, HAEFELI, W. E, BLASCHKE, T. F, HOFFMAN, B. B
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-12-1993
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Bradykinin - administration & dosage; Bradykinin - pharmacology; Disorders of blood lipids. Hyperlipoproteinemia; Dose-Response Relationship, Drug; Drug Resistance; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; Female; Humans; Hypercholesterolemia - drug therapy; Hypercholesterolemia - physiopathology; Indomethacin - pharmacology; Lovastatin - therapeutic use; Male; Medical sciences; Metabolic diseases; Middle Aged; Models, Cardiovascular; Nitric Oxide - physiology; Nitroglycerin - pharmacology; Vasodilation - drug effects; Vasodilation - physiology; Human; Pharmacologic test; Hypercholesterolemia; Bradykinin; Metabolic diseases; Exploration; Vein; Vasodilation
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.88.6.2754

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.
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%.
These results demonstrate that hypercholesterolemia in humans does not impair endothelium-derived relaxing factor-mediated venodilation.