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(Hypertension. 2002;39:209.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Preproendothelin-1 Gene Polymorphism Is Related to a Change in Vascular Reactivity in the Human Mammary Artery In Vitro

Marc Iglarz; Joëlle Benessiano; Ivan Philip; Sandrine Vuillaumier-Barrot; Sigismond Lasocki; Ulrich Hvass; Geneviève Durand; Jean-Marie Desmonts; Bernard I. Lévy; Daniel Henrion

From the Institut National de la Santé et de la Recherche Médicale (INSERM) U 541,IFR Circulation-Paris VII, Université Paris VII (M.I., D.H.), Paris, France; Service de Physiologie, Université Paris VII, AP-HP-Hôpital Lariboisière (B.I.L.), Paris, France; and Laboratoire de Biochimie (J.B., S.V-B., G.D.), Service d’Anesthésie-Réanimation (I.P., J-M.D.), and Service de Chirurgie Cardiaque (S.L., U.H.), AP-HP-Hôpital Xavier Bichat, Paris, France.

Correspondence to D. Henrion, PhD, INSERM U 541, 41 Bd de la Chapelle, 75475 Paris, cedex 10, France. E-mail daniel.henrion{at}inserm.lrb.ap-hop-paris.fr

A gene polymorphism of preproendothelin-1 (a G-to-T transversion that predicts a Lys/Asn change at codon 198) associated with an increased risk of hypertension has been recently described in patients carrying the T allele. No study has yet determined the impact of this polymorphism on vascular reactivity, although a functional role for endothelin-1 in the pathophysiology of hypertension has been clarified. At subthreshold concentrations, endothelin-1 and angiotensin II induce a potentiation of -adrenergic–dependent vascular tone caused by an increased sensitivity of the contractile apparatus to calcium. We investigated phenylephrine-induced tone and its amplification by endothelin-1 and angiotensin II in human mammary artery rings in vitro. Contractions to phenylephrine (0.1 to 100 µmol) and endothelin-1 (0.1 to 300 nmol) were not significantly different in rings from GT/TT (n=27) and GG (n=21) patients. A subthreshold concentration of endothelin-1 (10 pmol) potentiated a phenylephrine-induced contraction (eg, 44±12% increase in tone with phenylephrine 1 µmol/L, P<0.001) that was significantly higher in the GT/TT group than in the GG group (eg, 44±12% versus 82±11%, P<0.01). A similar effect on response to phenylephrine was observed with a subthreshold concentration of angiotensin II. We also found a higher response to calcium in arteries from GT/TT patients. Endothelium-dependent or -independent relaxations were unaffected by the genotype. These data suggest that the preproendothelin-1 gene polymorphism is associated with a higher potentiating effect of endothelin-1 and angiotensin II, probably in relation with higher calcium sensitivity. These changes in vascular reactivity might help to understand the relations between this polymorphism and cardiovascular disorders.

Key Words: blood vessels • polymorphism • endothelin • phenylephrine • angiotensin II

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