G894T polymorphism in the endothelial nitric oxide synthase gene is associated with an enhanced vascular responsiveness to phenylephrine

Background-Differences in vascular reactivity to phenylephrine (PE) respons iveness have been largely evidenced in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB), Because nitric oxide (NO) strongly affec ts modulation of the vascular tone in response to vasopressor agents, we hy pothesized that the G894T polymorphism of the endothelial NO synthase gene (eNOS) could be related to changes in the presser response to PE. Methods and Results-The protocol was performed in 68 patients undergoing co ronary artery bypass grafting (n = 33) or valve surgery (n = 35) in whom me an arterial pressure decreased below 65 mm Hg during normothermic CPB. Unde r 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 ind ividual doses of PE (25 to 500 mu g) The G894T polymorphism of the eNOS gen e 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), independen tly of possible confounding variables. Conclusions-These results evidenced an enhanced responsiveness to ol-adrene rgic stimulation in patients with the 894T allele in the eNOS gene.