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Influence of the M235T Polymorphism of Human Angiotensinogen (AGT) on Plasma AGT and Renin Concentrations after Ethinylestradiol Administration¹

Centre d’Investigations Cliniques 9201 (M.A., M.-C.H., T.T.G., J.M.) and Laboratoire de Biologie Moléculaire (X.J.), Assistance Publique des Hôpitaux de Paris (AP-HP) et INSERM, Hôpital Européen Georges Pompidou, 75908 Paris, France

Address all correspondence and requests for reprints to: Michel Azizi, Centre d’Investigations Cliniques 9201, Hôpital Européen Georges Pompidou, 20–40 rue Leblanc, 75908, Paris Cedex 15, France. E-mail: michel.azizi{at}egp.ap-hop-paris.fr

The T235 allele of the angiotensinogen (AGT) gene is associated with plasma AGT concentration and pregnancy-induced hypertension. The aim of this study was to compare changes in the circulating renin-angiotensin system after short-term (2 days) and repeated (7 days) administration of 50 µg ethinylestradiol (EE) in homozygous normotensive men (TT and MM). After repeated EE administration, renin stimulation was induced by a single oral dose of 40 mg furosemide, followed by 50 mg captopril, 12 h later. The short-term administration of EE did not induce a significant differential genotype-dependent increase in AGT concentration. In the 7-day study, TT subjects had higher peak plasma AGT concentrations than MM subjects. The more pronounced AGT increase in TT subjects resulted in similar plasma renin activity at a lower plasma active renin concentration, with a higher plasma renin activity/active renin ratio. The difference between genotypes in renin secretion resulted in readjustment of angiotensins production. In conclusion, the T235 allele of the AGT gene is associated with greater stimulation of AGT secretion in plasma after EE administration. In the short-term, complete readjustment of the circulating renin-angiotensin system occurs, through a decrease in renin release, which blunts the effects of the increase in AGT concentration.

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