Polymorphisms in the renin-angiotensin system and endothelium-dependent vasodilation in normotensive subjects.
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.
Kurland
L
L
Department of Medical Sciences, Uppsala University Hospital, Sweden.
Melhus
H
H
Sarabi
M
M
Millgård
J
J
Ljunghall
S
S
Lind
L
L
D000328:Adult; D000368:Aged; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*
D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D009599:Nitroprusside; D019405:Cytochrome P-450 CYP11B2; D007703:Peptidyl-Dipeptidase A