ANGIOTENSIN-CONVERTING ENZYME GENE POLYMORPHISM HAS NO INFLUENCE ON THE CIRCULATING RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM OR BLOOD-PRESSURE IN NORMOTENSIVE SUBJECTS

Background Angiotensin-converting enzyme (ACE) is involved in the meta bolism of two major vasoactive peptides, converting angiotensin (Ang) I into Ang II and inactivating bradykinin. An insertion/deletion (I/D) polymorphism is present in the 16th intron of the ACE gene and is str ongly associated with plasma and cellular ACE levels. Contrasting with the lack of relation between ACE gene polymorphism and blood pressure level, a large case-control study has shown that the deletion marker allele of the ACE gene was associated with an increased risk of myocar dial infarction. The pathophysiological link between ACE gene polymorp hism and cardiovascular events remains hypothetical. One hypothesis is that this polymorphism influences Ang II and bradykinin concentration s in the peripheral and/or local circulations through its effects on A CE levels in plasma and endothelial cells. The aim of this study was t o investigate the effect of the ACE gene I/D polymorphism on blood pre ssure, plasma active renin, and aldosterone regulation in normal subje cts. Methods and Results Twenty-four normotensive male volunteers homo zygous for the ACE I/D polymorphism (12 DD and 12 II) received a renin inhibitor infusion (remikiren 0.1 mg . kg(-1). h(-1) for 130 minutes) to suppress endogenous Ang I and Ang II production. Forty minutes aft er initiating the remikiren infusion, an exogenous Ang I infusion was begun and increased gradually every 15 minutes from 1 to 10 ng . kg(-1 ). min(-1). Median (range) plasma ACE levels (mU/mL) were 39 (32 to 57 ) and 24 (12 to 30) in the DD and II groups, respectively. Remikiren s uppressed plasma Ang I and Ang II, increased plasma active renin (from 23 +/- 12 to 154 +/- 161 pg/mL), decreased plasma aldosterone (from 1 06 +/- 42 to 82 +/- 33 pg/mL), and slightly decreased diastolic blood pressure (from -2.4 +/- 2.7 mm Hg). The blood pressure and hormonal re sponses to Ang I infusion after renin inhibition and the slope of the rise in plasma Ang II with increasing Ang I dose were identical in bot h groups, as was the plasma Ang I/Ang II ratio before (DD, 2.09 +/- 1. 04; II, 2.59 +/- 0.76) and after (DD, 0.15 +/- 0.13; II, 0.09 +/- 0.03 ) combined renin inhibitor and Ang I infusion. Conclusions Despite its association with a major difference in plasma ACE levels, the ACE VD polymorphism did not influence the Ang II and plasma aldosterone produ ction, plasma active renin decrease, or diastolic blood pressure incre ase induced by exogenous Ang I infusion, suggesting that ACE has no li miting influence on systemic Ang II generation and effects under these experimental conditions.