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Chronic treatment with progesterone but not medroxyprogesterone acetate restores the endothelial control of vascular tone in the mesenteric artery of ovariectomized rats

Chataigneau, Thierry PhD; Zerr, Murielle; Chataigneau, Marta PhD; Hudlett, Fréanderic; Hirn, Carole; Pernot, Fanny PhD; Schini-Kerth, Valéric Barbara PhD

doi: 10.1097/01.GME.0000097847.95550.E3
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Objective: To examine whether chronic administration of the natural hormone progesterone or a synthetic progestogen, medroxyprogesterone acetate, to ovariectomized rats affects the endothelial control of arterial tone in the isolated mesenteric artery.

Design: Sham-operated rats received a daily subcutaneous injection of solvent (sesame oil), whereas ovariectomized rats received either sesame oil, progesterone (22 mg kg−1/day), or medroxyprogesterone acetate (22 mg kg−1/day) for 4 weeks, according to their respective group.

Results: Phenylephrine-induced contractions were significantly increased (about 200% at 10 μM) by Nw-nitro-L-arginine, a nitric oxide synthase inhibitor, in intact mesenteric arterial rings from the sham-operated but not from the ovariectomized group. The progesterone but not the medroxyprogesterone treatment restored the potentiating effect of Nw-nitro-L-arginine on phenylephrine-induced contraction (about 180% at 10 μM). Contractions to phenylephrine were not affected by the combination of charybdotoxin plus apamin, two inhibitors of endothelium-derived hyperpolarizing factor-mediated responses, in all groups. Acetylcholine induced endothelium-dependent relaxations, which were partially inhibited by Nw-nitro-L-arginine and abolished by the combination of Nw-nitro-L-arginine plus charybdotoxin and apamin, in all groups. Acetylcholine induced similar charybdotoxin and apamin-sensitive hyperpolarizations in intact mesenteric artery segments from all groups.

Conclusions: Chronic administration of progesterone, but not medroxyprogesterone, to ovarictomized rats restores the endothelium-dependent attenuation of contractile responses to phenylephrine in mesenteric arterial rings through the endothelial formation of nitric oxide. Thus, an enhancement of the protective effect of endothelial cells on the arterial wall might contribute to the beneficial effect of certain progestogen-containing preparations during hormonal treatment.

This study examines whether chronic administration of progesterone or medroxyprogesterone acetate to ovariectomized rats affects endothelial control of vascular tone in the mesenteric artery. The results indicate that the progesterone treatment but not the medroxyprogesterone acetate treatment restores the endothelial control of vascular tone via the endothelial formation of nitric oxide.

From the Department of Pharmacology and Physico-Chemistry of Cellular and Molecular Interactions, College of Pharmacy, Louis Pasteur University, Illkirch, France.

Received May 27, 2003; revised and accepted September 4, 2003.

This study was supported by the Institut de Recherches Internationales Servier, Suresnes, France.

Address correspondence to: Prof. Valérie Barbara Schini-Kerth, UMR CNRS 7034, Faculté de Pharmacie, Université Louis Pasteur, F-67401 Illkirch, France. E-mail: schini@aspirine.u-strasbg.fr.

©2004The North American Menopause Society