Regulation of estrogen-induced uterine hyperemia and contractility in the guinea pig: cholinergic modulation of an alpha-adrenergic response.
The effects of estradiol (1 microgram: E-1) treatment on uterine hyperemia and uterine sensitivity to various biogenic compounds were evaluated in ovariectomized (OVX) animals treated with either sesame oil or E-1 for 3 days. The E-1 treatments induced significant elevations in uterine weight, blood flow, and alpha- and beta-receptor numbers as compared with oil-treated controls. In contrast, uterine norepinephrine (NE) levels were reduced in E-1-treated, OVX guinea pigs as compared with oil-treated controls. Uterine sensitivity and responsivity to NE (10(-6) M) and acetylcholine (ACH: 10(-8) M) were either comparable to, or enhanced, in E-1-treated animals as compared with controls. In particular, combined ACH-NE treatment induced a dramatic increase in contraction force in E-1-treated uteri as compared with uteri from oil-treated animals. The use of specific adrenergic alpha- (phentolamine: 10(-6) M) or beta- (propranolol: 10(-6) M) receptor blocking agents indicated that the estrogenic response was mediated via the alpha-adrenergic receptor complex. Since atropine (10(-8) M) effectively blocked the cholinergic accentuation of this uterine response, it is suggested that a cholinergic priming, or beta-receptor block, is necessary for the full expression of the alpha-adrenergic-mediated, estrogenic response in the guinea pig. The estrogen-associated increase in available alpha- and beta-receptors and depressed tissue NE levels probably account for both the hyperemic response and enhanced tissue sensitivity to biogenic compounds in the guinea pig.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000098:blood supply*
D011942:Receptors, Adrenergic, alpha; D004958:Estradiol; D001285:Atropine; D011433:Propranolol; D000109:Acetylcholine; D009638:Norepinephrine; D010646:Phentolamine