Effect of pregnancy and sex steroids on alpha 1-adrenoceptor mechanisms in the guinea-pig uterine vascular bed.
Adrenoceptor mechanisms in the extrinsic uterine arteries from late pregnant guinea-pigs were characterized pharmacologically and compared with contractile responses of uterine arteries from non-pregnant and oophorectomized control, progesterone and oestrogen treated animals. Pregnancy caused an increase in diameter of the arteries, more pronounced the more distal they were. There was no change in potassium-evoked maximum contractions during pregnancy. Noradrenaline (10 nM to 1 mM), in the presence of cocaine (1 microM) and propranolol (0.1 microM), induced concentration-dependent contractions of the arterial segments, with approximately similar pD2 values. The maximum responses (Emax) were significantly increased during pregnancy and hormone supplementation. Prazosin (10 nM to 1 microM), but not rauwolscine (10 nM to 1 microM), antagonized noradrenaline-evoked contractions of the arteries. Isoprenaline (10 nM to 1 microM), in the presence of prazosin (0.1 microM) and cocaine (1 microM), had no relaxant effect on arteries contracted submaximally by prostaglandin F2a (5 microM). Neither cocaine nor normetanephrine modified noradrenaline-evoked contractions of the uterine artery. The results indicate that guinea-pig uterine vasoconstriction is mediated by alpha 1-adrenoceptors while relaxant beta-adrenoceptor effects, neuronal and extraneuronal uptake mechanisms are of minor importance. The observed increase in Emax may be due either to an increase in the number of alpha 1-adrenoceptors or to an enhanced pharmaco-mechanical coupling, which conceivably is regulated by sex steroids since this response was reproduced in castrated animals by hormone supplementation.
Fallgren
B
B
Department of Zoophysiology, University of Lund, Sweden.
Bjellin
L
L
Edvinsson
L
L
D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D009647:Normetanephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011224:Prazosin / Q000493:pharmacokinetics; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000098:blood supply*; D015016:Yohimbine / Q000494:pharmacology
D012739:Gonadal Steroid Hormones; D011942:Receptors, Adrenergic, alpha; D009647:Normetanephrine; D015016:Yohimbine; D003042:Cocaine; D007545:Isoproterenol; D011188:Potassium; D009638:Norepinephrine; D011224:Prazosin