Effects of oral contraceptives on vascular endothelium in premenopausal women.
OBJECTIVE
Premenopausal women are protected against atherosclerosis by high plasma estrogen levels, which have been suggested to augment endothelial nitric oxide synthesis and to improve endothelial function. In contrast, premenopausal use of oral contraceptives is associated with an increased cardiovascular risk. We investigated the influence of oral contraception on endothelial function.


METHODS
Sixteen healthy premenopausal women with a mean age (+/-SD) of 27 +/- 3 years, 8 of whom used oral contraceptives and 8 of whom did not, were examined in a case-control study. Forearm plethysmography was used to measure changes of forearm blood flow in response to intra-arterial infusion of increasing doses of acetylcholine, sodium nitroprusside, and N (G)-monomethyl-L -arginine.


RESULTS
Endothelium-dependent vasodilatation (change from baseline after acetylcholine 48 microg/min) was similar between women with (828% +/- 137%) and without oral contraception (701% +/- 114%; P not significant), as was endothelium-independent vasodilatation (change from baseline after sodium nitroprusside 3200 ng/min, 271% +/- 38% vs 289% +/- 23%; P not significant). In contrast, inhibition of nitric oxide synthase with N (G)-monomethyl-L -arginine induced a significantly more marked decrease in blood flow among women with oral contraception than among those without at all dosages (change from baseline after 4-micromol/min N (G)-monomethyl-L -arginine, -26% +/- 3% vs -14% +/- 5%; P =.009 by analysis of variance).


CONCLUSIONS
Stimulated nitric oxide bioavailability remained unaffected in a group of premenopausal women receiving oral contraceptives. In contrast, basal nitric oxide production and release appeared to be enhanced by oral contraceptive use.
Department of Medicine IV, University of Erlangen-Nürnberg, Klinikum Nürnberg-Süd, Germany.
S
S
John
J
J
Jacobi
M P
MP
Schlaich
C
C
Delles
R E
RE
Schmieder
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D001783:Blood Flow Velocity; D016022:Case-Control Studies; D003277:Contraceptives, Oral, Combined / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D017697:Premenopause; D011374:Progesterone / Q000008:administration & dosage / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D003277:Contraceptives, Oral, Combined; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D004997:Ethinyl Estradiol; D011374:Progesterone; D019001:Nitric Oxide Synthase; D000109:Acetylcholine