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.


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.
Danser
A H
AH
Cardiovasculair Onderzoeksinstituut Erasmus Universiteit Rotterdam, The Netherlands. danser@farma.fgg.eur.nl
Deinum
J
J
Osterop
A P
AP
Admiraal
P J
PJ
Schalekamp
M A
MA
D000328:Adult; D000368:Aged; D000803:Angiotensin I / Q000097:blood / Q000378:metabolism*; D000804:Angiotensin II / Q000096:biosynthesis* / Q000097:blood; D004251:DNA Transposable Elements; D005260:Female; D005542:Forearm / Q000098:blood supply*; D017353:Gene Deletion; D006801:Humans; D007866:Leg / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics* / Q000502:physiology
D004251:DNA Transposable Elements; D000804:Angiotensin II; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A