Chronic treatment with progesterone but not medroxyprogesterone acetate restores the endothelial control of vascular tone in the mesenteric artery of ovariectomized rats.
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.
Chataigneau
Thierry
T
Department of Pharmacology and Physico-Chemistry of Cellular and Molecular Interactions, College of Pharmacy, Louis Pasteur University, Illkirch, France.
Zerr
Murielle
M
Chataigneau
Marta
M
Hudlett
Fréanderic
F
Hirn
Carole
C
Pernot
Fanny
F
Schini-Kerth
Valéric Barbara
VB
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
D010656:Phenylephrine; D011374:Progesterone; D017258:Medroxyprogesterone Acetate