The deletion genotype of the angiotensin I-converting enzyme is associated with an increased vascular reactivity in vivo and in vitro

OBJECTIVES To define a link between the deletion genotype (DD) and vascular reactivity, we studied in vivo and in vitro phenylephrine (PE)-induced tone and the effect of angiotensin II (AII) at physiological (subthreshold) concentrations on PE-induced tone. BACKGROUND The deletion allele (D) of the angiotensin I-converting enzyme (ACE) has been associated with a higher circulating and cellular ACE activity and possibly with, some cardiovascular diseases. METHODS During cardiac surgery PE-induced contraction was studied in patients with excessive hypotension. In parallel, excess material of internal mammary artery, isolated from patients operated for bypass surgery, was mounted in an organ chamber, in vitro, for isometric vascular wall force measurement. RESULTS In patients under extracorporeal circulation, PE (25 to 150 mu g) induced higher contractions in patients with the DD genotype (e.g., with PE 75 mu g: 20.3 +/- 2.9 vs. 11.5 +/- 2.5 mm Hg/ml per min, DD vs. II/ID, n = 15 vs. 30, p < 0.03). In the mammary artery, in vitro, contractions to PE (0.1 to 100 mu mol/liter) or AII (1 or 100 nmol/liter) were not affected by the genotype. Angiotensin II (10 pmol/liter) significantly potentiated PE (1 mu mol/liter)induced contraction in both groups. Potentiation of PE-induced tone by AII was significantly higher in the DD than in the II/ID group. CONCLUSIONS The DD genotype was associated with an increased reactivity to PE in vivo and potentiating effect of exogenous AII in vitro. The higher response to PE in vivo might reflect a higher potentiation by endogenous AII. These data should be considered to understand possible link(s) between cardiovascular disorders and the ACE gene polymorphism. (J Am Coil Cardiol 1999;34:830-6) (C) 1999 by the American College of Cardiology.