Human vascular reactivity and polymorphisms of the angiotensin-converting enzyme and the angiotensin type 1 receptor genes.
The D allele of the insertion (I)/deletion (D) polymorphism in the angiotensin-converting enzyme (ACE) gene and the C allele of the A1166-C polymorphism in the angiotensin II type 1 receptor (AGT1R) gene have been associated with altered vascular structure and with an increased risk of myocardial infarction. The aim of this study was to determine whether differences in vascular function could be demonstrated to link the previously described changes in structure and the disease outcome. 70 subjects were recruited at random from patients undergoing colonic resection, resistance arteries were excised and were mounted in a small vessel wire myograph. Vasomotor responses to potassium chloride, noradrenaline, prostaglandin F(2alpha), angiotensin I, angiotensin II, acetylcholine and substance P were performed in 30 subjects. Genotype was established in a blinded fashion after completion of myography. To exclude the possibility of masking of genetic influence by non-ACE conversion of angiotensin I, vasomotor responses were then performed to proline(10)-angiotensin I in a further 30 subjects and to angiotensin I in the presence of chymostatin in a further 10 subjects. No significant effect of the I/D polymorphism of the ACE gene was seen on vasomotor function. The C allele of the AGT1R gene was associated with an increase in sensitivity to prostaglandin F(2alpha) but not with alteration to the other vasoactive agents studied. The I/D ACE and A1166-C AGT1 receptor polymorphism do not appear to result in differences in vasomotor function in isolated human mesenteric resistance arterioles in subjects without evidence of underlying hypertensive or cardiovascular disease.
Steeds
R P
RP
Department of Cardiology, Royal Hallamshire Hospital, Sheffield, UK.
Toole
L O
LO
Channer
K S
KS
Morice
A H
AH
D000368:Aged; D000803:Angiotensin I / Q000378:metabolism / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011945:Receptors, Angiotensin / Q000235:genetics*; D014655:Vascular Resistance / Q000235:genetics
D011945:Receptors, Angiotensin; D000803:Angiotensin I; D015237:Dinoprost; D007703:Peptidyl-Dipeptidase A