Responsiveness to bradykinin in veins of hypercholesterolemic humans.
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.


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
G V
GV
Division of Clinical Pharmacology, Stanford University Medical Center, CA 94305-5113.
Bushell
E
E
Haefeli
W E
WE
Blaschke
T F
TF
Hoffman
B B
BB
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008148:Lovastatin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular; D009569:Nitric Oxide / Q000502:physiology; D005996:Nitroglycerin / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D009569:Nitric Oxide; D008148:Lovastatin; D005996:Nitroglycerin; D001920:Bradykinin; D007213:Indomethacin