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 acc ounts 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 presser effect s of angiotensin (Ang) I in DD compared with II subjects are inconsistent, because enhanced conversion in DD subjects may have been masked by a decrea sed responsiveness to Ang II. Here we quantify ACE genotype-related Ang I t o Ang II conversion in the human forearm and leg using non-presser I-125-An g I infusions. Design and methods Infusions were given to 12 women and 17 men (age 24-67 y ears) who were undergoing renal vein sampling followed by renal angiography for diagnostic purposes. I-125-Ang I was infused for 20 min into the right antecubital vein, and blood samples for the measurement of I-125-labelled and endogenous Ang I and Ang II were taken from the aorta, the left antecub ital vein and a femoral vein under steady-state conditions. Genotype freque ncies were determined by polymerase chain reaction. Results Fractional conversion (i.e. the percentage of arterially delivered I-125-Ang I that is converted to I-125-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 ra tio (a measure of ACE activity) were observed at the three sampling sites. Conclusions Regional Ang I to Ang II conversion does not parallel the previ ously described D allele-related differences in ACE concentration, suggesti ng that effects other than enhanced conversion may underlie the reported as sociations between the D allele and various cardiovascular diseases. J Hype rtens 1999, 17:1867-1872 (C) Lippincott Williams & Wilkins.