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) 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.


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 micrograms). 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 alpha-adrenergic stimulation in patients with the 894T allele in the eNOS gene.
Philip
I
I
Laboratoire de Biochimie, Département d'Anesthésie Réanimation, Hôpital Bichat, Paris, France.
Plantefeve
G
G
Vuillaumier-Barrot
S
S
Vicaut
E
E
LeMarie
C
C
Henrion
D
D
Poirier
O
O
Levy
B I
BI
Desmonts
J M
JM
Durand
G
G
Benessiano
J
J
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage*; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D001026:Coronary Artery Bypass; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005838:Genotype; D006801:Humans; D007432:Intraoperative Period; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D010656:Phenylephrine / Q000008:administration & dosage*; D017354:Point Mutation; D011110:Polymorphism, Genetic; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D010656:Phenylephrine; D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III