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Background The renin-angiotensin system is involved in blood pressure regulation. The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is known to be associated with variation of plasma and cellular ACE concentrations. Furthermore, changes in arterial function have been suggested to be associated to the DD genotype. The aim of the study was to investigate the arterial vascular response to a physiologic stimulus (i.e., flow) according to the I/D ACE gene polymorphism. Methods Sixty patients scheduled for coronary artery bypass grafting (n = 24) or valve surgery (n = 36) under normothermic cardiopulmonary bypass were genotyped in a blind manner by polymerase chain reaction. Mean arterial pressure was measured at pump flows ranging from 1 to 3 l x min(-1) x m (-2) by 0.25 l x min(-1) x m(-2) step each 15 s, to obtain a pressure-flow relation. Independent factors associated with the variation of the slope of the pressure-flow relation curve were assessed by multivariate analysis. Results We found a D allelic frequency of 0.54. Patients were separated in two groups (DD, n = 16; ID/II, n = 44). There were no significant difference with regard to preoperative and intraoperative data between the two groups. DD patients had their pressure-flow relation curves shifted upward (with higher pressures as flow increased), indicating a lesser decrease in vascular resistance. Furthermore, DD genotype was the only independent predictor of the slope of the curves (21.5 +/- 4.2 vs. 18.1 +/- 5 mmHg/[l x min(-1) x m(-2)] for DD and ID/II, respectively; P = 0.02; values are mean +/-SD). Conclusion These results show that vasomotor properties are influenced by the I/D polymorphism of the ACE gene.

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 α-adrenergic stimulation in patients with the 894T allele in the eNOS gene.