Endothelium-dependent vasodilation in conduit and resistance vessels in relation to the endothelial nitric oxide synthase gene

• Published in: Journal of human hypertension Vol. 22; no. 8; pp. 569 - 578
• Main Authors: Ingelsson, E, Syvänen, A-C, Lind, L
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-08-2008; Nature Publishing; Nature Publishing Group
• Subjects: Aged; Antidiabetics; Antihypertensives; Arterial hypertension. Arterial hypotension; Arteries; Biological and medical sciences; Blood and lymphatic vessels; Blood pressure; Blood vessels; Blood vessels and receptors; Body mass index; Brachial Artery - diagnostic imaging; Brachial Artery - physiopathology; Cardiology. Vascular system; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - genetics; Cardiovascular Diseases - physiopathology; Cholesterol; Coronary artery disease; Diabetes mellitus; Dilatation; DNA - genetics; endothelial function; Endothelium; Endothelium, Vascular - metabolism; Endothelium, Vascular - physiopathology; Epidemiology; Female; Follow-Up Studies; Forearm; Fundamental and applied biological sciences. Psychology; Gene Frequency; Genetic aspects; Genetic diversity; Genetic Predisposition to Disease; genetics; Haplotypes; Health Administration; Heart diseases; Humans; Male; Medical sciences; MEDICIN; MEDICINE; Medicine & Public Health; Nitric oxide; Nitric Oxide Synthase Type III - genetics; Nitric-oxide synthase; NOS3 protein; original-article; Physiological aspects; Polymorphism, Genetic; Prospective Studies; Public Health; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Ultrasonography; Vascular Resistance - genetics; Vasodilation; Vasodilation - genetics; Veins & arteries; Vertebrates: cardiovascular system; Sweden; endothelial function; nitric oxide; genetics; Hypertension; Enzyme; Nitric oxide; Cardiovascular disease; Oxidoreductases; Nitric-oxide synthase; Vasodilation; Endothelium
• ISSN: 0950-9240; 1476-5527; 1476-5527
• DOI: 10.1038/jhh.2008.37

Single nucleotide polymorphisms (SNPs) in the endothelial nitric oxide synthase (
NOS3
) gene have been related to endothelium-dependent vasodilation in either conduit or resistance arteries with divergent results. In the Prospective Study of the Vasculature in Uppsala Seniors study, 959 participants aged 70 (51% men) were evaluated with brachial artery ultrasound to assess flow-mediated vasodilation (FMD; reflecting conduit arteries) and invasive forearm technique with intrabrachial infusion of acetylcholine (endothelium-dependent vasodilation (EDV); reflecting resistance arteries). The 23 SNPs analysed by minisequencing captured >90% of the common genetic variation in the
NOS3
gene, using the HapMap population of European ancestry (CEU) as reference. One SNP (Glu298Asp) was related to FMD (nominal
P
=0.0018), but not to EDV (nominal
P
=0.76) after adjustment for sex, systolic blood pressure, diastolic blood pressure, pulse rate, antihypertensive treatment, total cholesterol, high-density cholesterol, lipid-lowering medication, fasting glucose, antidiabetic medication, body mass index, current smoking and prior diagnosis of cardiovascular disease. This relation was significant in both men and women in sex-specific analyses, and remained significant after adjusting for multiple testing (empirical
P
=0.029 from bootstrap resampling). None of the constructed haplotypes were related to vasodilation. The Glu298Asp SNP in the
NOS3
gene was related to endothelium-dependent vasodilation in conduit, but not in resistance arteries. This SNP has previously been related to coronary heart disease, and our findings should stimulate to replication and exploration of the association of
NOS3
variation with endothelial function in other settings.