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 angioten sin-converting enzyme (ACE) gene and the C allele of the A1166-C polymorphi sm in the angiotensin II type 1 receptor (AGT1R) gene have been associated with altered vascular structure and with an increased risk of myocardial in farction. The aim of this study was to determine whether differences in vas cular function could be demonstrated to link the previously described chang es in structure and the disease outcome. 70 subjects were recruited at rand om from patients undergoing colonic resection, resistance arteries were exc ised and were mounted in a small vessel wire myograph. Vasomotor responses to potassium chloride, noradrenaline, prostaglandin F-2 alpha, angiotensin I, angiotensin II, acetylcholine and substance P were performed in 30 subje cts, Genotype was established in a blinded fashion after completion of myog raphy. To exclude the possibility of masking of genetic influence by non-AC E conversion of angiotensin I, vasomotor responses were then performed to p roline(10)-angiotensin I in a further 30 subjects and to angiotensin I in t he 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-2 alpha but not with alteration to the other vasoactive agents studied. The I/D ACE and A1166-C AGT1 receptor polymorphism do not a ppear to result in differences in vasomotor function in isolated human mese nteric resistance arterioles in subjects without evidence of underlying hyp ertensive or cardiovascular disease. Copyright (C) 1999 S. Karger AG. Basel .