Polymorphisms in the renin-angiotensin system and endothelium-dependent vasodilation in normotensive subjects

Background Our aim was to test the hypothesis that genes encoding component s in the renin-angiotensin system influence endothelial vasodilatory functi on. Methods In 59 apparently healthy, normotensive individuals, endothelium-dep endent (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 AC E insertion (I)/deletion (D) polymorphism, the T174M and M235T angiotensino gen restriction fragments length polymorphisms, the angiotensin II receptor type I (AT1R) A1166C, and the aldosterone synthase gene (CYP11B2) C-344T p olymorphisms 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 reducti on in endothelium-dependent vasodilation was observed in the subjects (n = 9) with the ACE D allele and the angiotensinogen T174M genotype (P<0.05). S ubjects 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 angi otensinogen T174M genotype are associated with a reduced EDV. This together with the observation that the AC AT1R genotype is associated with a reduct ion in both EDV and EIDV, supports the hypothesis that endothelial vasodila tory function is influenced by genes in the renin-angiotensinogen system.