Angiotensin I to angiotensin II conversion in the human forearm and leg. Effect of the angiotensin converting enzyme gene insertion/deletion polymorphism

OBJECTIVE: The angiotensin-converting enzyme (ACE) gene I/D polymorphism accounts for part of the variation in ACE concentration; subjects with one or two D alleles have approximately 25 and 50% higher ACE levels, respectively, than subjects with two I alleles. Data from studies on the pressor effects of angiotensin (Ang) I in DD compared with II subjects are inconsistent, because enhanced conversion in DD subjects may have been masked by a decreased responsiveness to Ang II. Here we quantify ACE genotype-related Ang I to Ang II conversion in the human forearm and leg using non-pressor 125I-Ang I infusions. DESIGN AND METHODS: Infusions were given to 12 women and 17 men (age 24-67 years) who were undergoing renal vein sampling followed by renal angiography for diagnostic purposes. 125I-Ang I was infused for 20 min into the right antecubital vein, and blood samples for the measurement of 125I-labelled and endogenous Ang I and Ang II were taken from the aorta, the left antecubital vein and a femoral vein under steady-state conditions. Genotype frequencies were determined by polymerase chain reaction. RESULTS: Fractional conversion (i.e. the percentage of arterially delivered 125I-Ang I that is converted to 125I-Ang II) in the forearm (38+/-4, 30+/-3 and 31+/-6% in 8 II, 16 ID and 5 DD subjects, respectively; mean +/- SEM) and leg (52+/-4, 48+/-3 and 42+/-5%) was similar in all three groups. In addition, no genotype-related differences in plasma Ang II/I ratio (a measure of ACE activity) were observed at the three sampling sites. CONCLUSIONS: Regional Ang I to Ang II conversion does not parallel the previously described D allele-related differences in ACE concentration, suggesting that effects other than enhanced conversion may underlie the reported associations between the D allele and various cardiovascular diseases.