Responsiveness to bradykinin in veins of hypercholesterolemic humans.

Abstract

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.

• Authors: G V Bedarida, E Bushell, W E Haefeli, T F Blaschke, B B Hoffman
• Journal: Circulation (Circulation) Vol. 88 Issue 6 Pg. 2754-61 (Dec 1993) ISSN: 0009-7322 [Print] United States
• PMID: 8252688 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Nitric Oxide
• Lovastatin
• Nitroglycerin
• Bradykinin
• Indomethacin

Topics

• Adult
• Aged
• Aged, 80 and over
• Bradykinin (administration & dosage, pharmacology)
• Dose-Response Relationship, Drug
• Drug Resistance
• Endothelium, Vascular (drug effects, physiopathology)
• Female
• Humans
• Hypercholesterolemia (drug therapy, physiopathology)
• Indomethacin (pharmacology)
• Lovastatin (therapeutic use)
• Male
• Middle Aged
• Models, Cardiovascular
• Nitric Oxide (physiology)
• Nitroglycerin (pharmacology)
• Vasodilation (drug effects, physiology)