The Glu298Asp polymorphism of the NOS 3 gene as a determinant of the baseline production of nitric oxide.
Publication year
2002Source
Journal of Hypertension, 20, 10, (2002), pp. 2023-7ISSN
Publication type
Article / Letter to editor
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Organization
Internal Medicine
Nephrology
Pharmacology-Toxicology
Journal title
Journal of Hypertension
Volume
vol. 20
Issue
iss. 10
Page start
p. 2023
Page end
p. 7
Subject
Effects and kinetics of drugs in kidney and blood vessels; Hypertension and Circulation; Pathophysiology, immunology and treatment of renal disease.; Effecten en lotgevallen van geneesmiddelen in nier en bloedvaten; Hypertensie en circulatie; Pathofysiologie, immunologie en behandeling van nieraandoeningenAbstract
RATIONALE: The endothelial nitric oxide synthase Glu298Asp polymorphism has been suggested to play a role in the development of hypertension, atherosclerosis and coronary artery disease. OBJECTIVE: To investigate functional differences between the various genotypes with respect to basal nitric oxide (NO) production, we estimated the response to endothelial NO synthase (ecNOS) inhibition by infusion of increasing doses of N(G)-monomethyl-L-arginine (L-NMMA) into the brachial artery during venous occlusion plethysmography. METHODS: In 41 healthy subjects forearm blood flow responses to intra-arterial infusion of increasing doses of L-NMMA (0.05, 0.1 and 0.2 mg/min per dl) and norepinephrine (10, 20 and 40 ng/min per dl) were measured. The genotype of the ecNOS Glu298Asp polymorphism was assessed. RESULTS: Nineteen subjects had the Glu/Glu genotype, 19 subjects had the Glu/Asp genotype and three subjects had the Asp/Asp genotype. Groups were comparable concerning demographic, hemodynamic and possible confounding factors. Subjects with the Asp allele showed a reduced response to infusion of L-NMMA as compared to subjects with the Glu/Glu genotype (ANOVA, = 0.01). There was no significant difference in the response to infusion of the NO-independent vasoconstrictor, norepinephrine, between both groups. CONCLUSIONS: The ecNOS Glu298Asp polymorphism is associated with reduced basal NO production and might therefore have functional implications in the development of atherosclerosis or hypertension.
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- Academic publications [238586]
- Faculty of Medical Sciences [90409]
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