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CLINICAL STUDIES

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

Daniel Henrion, PhD^a, Joelle Benessiano, PhD^*, Ivan Philip, MD^#, Sandrine Vuillaumier-Barrot, PhD^*, Marc Iglarz, BSc^*, Gaetan Plantefève, MD^#, Didier Chatel, MD, Ulrich Hvass, MD, Geneviève Durand, PhD^*, Jean-Marie Desmonts, MD^#, Philippe Amouyel, MD^** and Bernard I. Lévy, MD, PhD^a

^a Institut National de la Santé et de la Recherche Médicale (INSERM) U 141, IFR Circulation, Université Paris VII, Hôpital Lariboisière, Paris, France
^* Laboratoire de Biochimie, Hôpital Xavier Bichat, Paris, France
^# Service d’Anesthésie-Réanimation, Hôpital Xavier Bichat, Paris, France
Service de Chirurgie Cardiaque, Hôpital Xavier Bichat, Paris, France
^** Service d’Epidémiologie et de Santé Publique, Institut Pasteur, Lille, France

Manuscript received May 28, 1998; revised manuscript received April 16, 1999, accepted June 3, 1999.

Reprint requests and correspondence: D. Henrion, PHD, INSERM U 141, 41 Bd de la Chapelle, 75475 Paris, Cedex 10, France
daniel.henrion{at}inserm.lrb.ap-hop-paris.fr

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 µg) induced higher contractions in patients with the DD genotype (e.g., with PE 75 µg: 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 µmol/liter) or AII (1 or 100 nmol/liter) were not affected by the genotype. Angiotensin II (10 pmol/liter) significantly potentiated PE (1 µmol/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.

Abbreviations and Acronyms   ACE = angiotensin I-converting enzyme   AII = angiotensin II   CPB = cardiopulmonary bypass   DD = deletion genotype   DRC = dose-response curve   I = insertion   MAP = mean arterial pressure   PE = phenylephrine

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