Polymorphisms in the renin-angiotensin system and endothelium-dependent vasodilation in normotensive subjects
2001 (English)In: Clinical Physiology, ISSN 0144-5979, Vol. 21, no 3, 343-349 p.Article in journal (Refereed) Published
BACKGROUND: Our aim was to test the hypothesis that genes encoding components in the renin-angiotensin system influence endothelial vasodilatory function.
METHODS: In 59 apparently healthy, normotensive individuals, endothelium-dependent vasodilation (EDV) and endothelial-independent vasodilation (EIDV) was evaluated by infusing metacholine and sodium nitroprusside into the brachial artery. Forearm blood flow was measured by venous occlusion plethysmography. The ACE insertion (I)/deletion (D) polymorphism, the T174M and M235T angiotensinogen restriction fragments length polymorphisms, the angiotensin II receptor type 1 (AT1R) A1166C, and the aldosterone synthase gene (CYP11B2) C-344T polymorphisms were analysed.
RESULTS: When analysing the ACE, the two angiotensinogen and the aldosterone synthase CYP11B2 genotypes independently, no significant association with endothelial vasodilatory function was found. However, a significant reduction in endothelium-dependent vasodilation was observed in the subjects (n=9) with the ACE D allele and the angiotensinogen T174M genotype (P<0.05). Subjects with the AT1R genotype AC showed a reduction in both EDV (P=0.05) and EIDV (P=0.04) when compared with those with the AA genotype.
CONCLUSIONS: The subjects with the ACE D allele in combination with the angiotensinogen T174M genotype are associated with a reduced EDV. This together with the observation that the AC AT1R genotype is associated with a reduction in both EDV and EIDV, supports the hypothesis that endothelial vasodilatory function is influenced by genes in the renin-angiotensinogen system.
Place, publisher, year, edition, pages
2001. Vol. 21, no 3, 343-349 p.
Adult, Aged, Aldosterone Synthase/genetics, Endothelium, Vascular/*physiology, Female, Gene Deletion, Humans, Male, Middle Aged, Nitroprusside/administration & dosage/pharmacology, Peptidyl-Dipeptidase A/*genetics, Polymorphism; Genetic, Polymorphism, Restriction Fragment Length, Receptor, Angiotensin, Type 1; Receptor; Angiotensin; Type 2, Receptors; Angiotensin/genetics, Renin-Angiotensin System/*genetics
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-73093DOI: 10.1046/j.1365-2281.2001.00336.xPubMedID: 11380534OAI: oai:DiVA.org:uu-73093DiVA: diva2:101004