Vasoreactivity in Carriers of Genetic Polymorphisms

Endothelium-Dependent Vasoreactivity in Nitric Oxide Synthase Gene (Glu298Asp) Polymorphism: Studies in Healthy Volunteers

The objective of the study is to assess the impact of genetic variation (especially polymorphisms of the gene coding endothelial nitric oxide synthase (eNOS) and the bradykinin B2 receptor gene) on venous and arterial responsiveness to vasodilators in healthy individuals without cardiovascular risk factors.

Study I: Using the dorsal hand vein compliance technique dose-response curves to bradykinin and sodium nitroprusside will be obtained in healthy volunteers during preconstriction with phenylephrine and after pretreatment with a single dose of 500 mg i.v. acetylsalicylic acid.

Study II: Using venous occlusion plethysmography dose-response curves to acetylcholine, sodium nitroprusside and L-NG-monomethyl-arginine (L-NMMA) will be obtained in healthy volunteers pretreated with a single dose of 500mg i.v. acetylsalicylic acid.

Inclusion Criteria:

• age: 18 - 70
• gender: male
• good state of health

Exclusion Criteria:

• known condition causing endothelial dysfunction (e.g. diabetes, hyperlipidaemia, arterial hypertension, smoking, homocysteinemia)
• regular medication and/or treatment with drugs within the last 4-6 weeks (exclusion has to be decided in each case)
• acute or chronic illness
• methylxanthines and alcohol during 12 hours before the study
• nicotine during 1 year before the study
• drug and/or alcohol abuse
• pregnancy or lactation