(Circulation. 1999;99:3096-3098.)
© 1999 American Heart Association, Inc.
Brief Rapid Communications |
G894T Polymorphism in the Endothelial Nitric Oxide Synthase Gene Is Associated With an Enhanced Vascular Responsiveness to Phenylephrine
From the Laboratoire de Biochimie (S.V.-B., C.L., G.D., J.B.) and Département d'Anesthésie Réanimation (I.P., G.P., J.M.D.), Hôpital Bichat, Paris, France; INSERM U141 (E.V., D.H., B.I.L.), Hôpital Lariboisière, Paris, France; and INSERM SC7 (O.P.), Paris, France.
Background—Differences in vascular reactivity to phenylephrine (PE) responsiveness have been largely evidenced in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Because nitric oxide (NO) strongly affects modulation of the vascular tone in response to vasopressor agents, we hypothesized that the G894T polymorphism of the endothelial NO synthase gene (eNOS) could be related to changes in the pressor response to PE.
Methods and Results—The protocol was performed in 68 patients undergoing coronary artery bypass grafting (n=33) or valve surgery (n=35) in whom mean arterial pressure decreased below 65 mm Hg during normothermic CPB. Under constant and nonpulsatile pump flow conditions (2 to 2.4 L · min-1 · m-2), a PE dose-response curve was generated by the cumulative injection of individual doses of PE (25 to 500 µg). The G894T polymorphism of the eNOS gene was determined, and 3 groups were defined according to genotype (TT, GT, and GG). Groups were similar with regard to perioperative characteristics. The PE dose-dependent response was significantly higher in the allele 894T carriers (TT and GT) than in the homozygote GG group (P=0.02), independently of possible confounding variables.
Conclusions—These results evidenced an enhanced responsiveness to
-adrenergic stimulation in patients with the 894T allele in the
eNOS gene.
Key Words: nitric oxide • endothelium • genes • receptors, adrenergic, alpha • vasoconstriction
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