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Polymorphisms in the renin-angiotensin system and endothelium-dependent vasodilation in normotensive subjects
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Akut- och internmedicin)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Clinical pharmacogenetics and osteoporosis)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Akut- och internmedicin)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Akut- och internmedicin)
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2001 (English)In: Clinical Physiology, ISSN 0144-5979, E-ISSN 1365-2281, Vol. 21, no 3, 343-349 p.Article in journal (Refereed) Published
Abstract [en]

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.
Keyword [en]
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
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-73093DOI: 10.1046/j.1365-2281.2001.00336.xPubMedID: 11380534OAI: oai:DiVA.org:uu-73093DiVA: diva2:101004
Available from: 2005-05-31 Created: 2005-05-31 Last updated: 2017-12-14Bibliographically approved

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Melhus, Håkan

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