title: Chronic treatment with progesterone but not medroxyprogesterone acetate restores the endothelial control of vascular tone in the mesenteric artery of ovariectomized rats.
abstract: 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.
  
  
  METHODS
  Sham-operated rats received a daily subcutaneous injection of solvent (sesame oil), whereas ovariectomized rats received either sesame oil, progesterone (22 mg kg/day), or medroxyprogesterone acetate (22 mg kg/day) for 4 weeks, according to their respective group.
  
  
  RESULTS
  Phenylephrine-induced contractions were significantly increased (about 200% at 10 microM) by N-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 N-nitro-L-arginine on phenylephrine-induced contraction (about 180% at 10 microM). 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 N-nitro-L-arginine and abolished by the combination of N-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.
authors.affiliation: Department of Pharmacology and Physico-Chemistry of Cellular and Molecular Interactions, College of Pharmacy, Louis Pasteur University, Illkirch, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Chataigneau
authors.forename: Murielle
authors.initials: M
authors.lastname: Zerr
authors.forename: Marta
authors.initials: M
authors.lastname: Chataigneau
authors.forename: Fréanderic
authors.initials: F
authors.lastname: Hudlett
authors.forename: Carole
authors.initials: C
authors.lastname: Hirn
authors.forename: Fanny
authors.initials: F
authors.lastname: Pernot
authors.forename: Valéric Barbara
authors.initials: VB
authors.lastname: Schini-Kerth
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D007279:Injections, Subcutaneous; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage / Q000494:pharmacology*; D008638:Mesenteric Arteries / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects; D010052:Ovariectomy; D010656:Phenylephrine; D011374:Progesterone / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D010656:Phenylephrine; D011374:Progesterone; D017258:Medroxyprogesterone Acetate