Medroxyprogesterone acetate does not antagonize estrogen-induced increases in endothelium-dependent vasodilation: potential clinical implications.
OBJECTIVE
Determine the effect of combined 17beta-estradiol benzoate (E2) and medroxyprogesterone acetate (MPA) administration on endothelium-dependent vasorelaxation to acetylcholine (ACh).


METHODS
Prospective, ex vivo study.


METHODS
Academic research laboratory.


METHODS
Mature female rats.


METHODS
Ovariectomized rats received one of the following interventions daily for 3 days: [1] corn oil via IM injection, [2] E2 (20 microg/kg IM), or [3] E2 (20 microg/kg IM) and MPA (10 mg/kg IM).


METHODS
Basal release of nitric oxide (NO) and endothelium-dependent and endothelium-independent vasodilation from thoracic aortas obtained from each group.


RESULTS
Estradiol treatment potentiated the endothelium-dependent relaxation to ACh when compared with the control group. Administration of MPA with E2 did not antagonize the beneficial effect of E2 on endothelium-dependent relaxation. Estradiol treatment alone or in combination with MPA did not affect endothelium-independent vasodilation as compared with the case of the control group. Administration of E2 resulted in increased basal NO release (assessed indirectly by measuring the constrictor response to N(G)-nitro-L-arginine [methyl ester (L-NAME)]) when compared with the case of the control group, and the addition of MPA to E2 did not alter the effect of E2 on basal NO release.


CONCLUSIONS
Estradiol potentiates endothelium-dependent relaxant responses and increases basal endothelial NO release. Medroxyprogesterone acetate does not antagonize these effects of E2.
Dinh
Hillary
H
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California, Los Angeles, California 90095-1735, USA.
Nathan
Lauren
L
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D045167:Progesterone Congeners / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D004338:Drug Combinations; D045167:Progesterone Congeners; D014665:Vasodilator Agents; D009569:Nitric Oxide; D004958:Estradiol; D017258:Medroxyprogesterone Acetate; D005996:Nitroglycerin; D000109:Acetylcholine