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PIII‐25
Author(s) -
Lang C. C.,
Chan S.,
Godfrey V.,
Butler R.,
Cassidy A. J.,
Fardon T.,
Choy A.,
Struthers A. D.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.233
Subject(s) - enos , vasodilation , sodium nitroprusside , endothelial dysfunction , medicine , endocrinology , endothelium , genotype , gene polymorphism , nitric oxide , pharmacology , biology , gene , nitric oxide synthase , genetics
BACKGROUND The Glu298Asp polymorphism of the endothelial nitric oxide synthase (eNOS) gene has been linked to cardiovascular disease. However, the functional consequences of this polymorphism have not been fully defined. Our aim was to investigate if this polymorphism is functionally relevant in healthy humans by having an effect on endothelial‐dependent vasodilatation. METHODS Endothelial function was assessed in 68 normal volunteers (aged 18–44y) by bilateral forearm venous occlusion plethysmography with intra‐arterial infusions of increasing doses of acetylcholine for endothelial dependent vasodilatation, sodium nitroprusside and verapamil for endothelial independent vasodilatation. Blood was genotyped by polymerase chain reaction and Ban II digestion. RESULTS There were 3 genotypes: homozygous for the Glu298 variant (GG), homozygous for the Asp298 variant (TT) and heterozygous (GT). The TT genotype's vasodilatory response to the endothelial‐dependent vasodilator acetylcholine was lower than the GG variant (p=0.04) and GT variant (p=0.08) (Fig). No differences were found between the GG and GT groups (p=NS). There was also no effect of eNOS genotype on the response to the endothelial‐independent vasodilators. CONCLUSION The Asp298 variant of the eNOS gene is associated with a blunted endothelial‐dependent vasodilation in healthy subjects. These findings may provide an important insight into the pathophysiology of endothelial dysfunction in cardiovascular diseases.Clinical Pharmacology & Therapeutics (2005) 79 , P65–P65; doi: 10.1016/j.clpt.2005.12.233