title: The influence of oestrogen and oestrogen metabolites on the sensitivity of the isolated rabbit aorta to catecholamines.
abstract: In the present study the influence of oestradiol, catechol oestrogens, and O-methylated oestrogens was determined on the contractile responses of the isolated rabbit aorta to (-)-adrenaline. Oestradiol (40 mumol/l), 2-hydroxyoestradiol (2OHE2) (20 mumol/l), and 2-methoxyoestradiol (2MeOE2) (20 mumol/l) all sensitized the rabbit aorta to contractile responses to (-)-adrenaline. Similarly, the 2-hydroxy and 2-methoxy derivatives of oestrone and oestriol also sensitized the aorta to (-)-adrenaline-induced contractions. The largest degree of sensitization was seen in the presence of the 2-methoxysteroids. Oestradiol and 2OHE2 did not increase responses of the aorta to (-)-noradrenaline, while slight potentiation of contraction was seen in the presence of 2MeOE3. The potentiating effect of 2OHE2 on contractile responses to (-)-adrenaline was abolished by prior treatment of the tissue with a COMT inhibitor (U-0521, 55 mumol/l). Conversely, pretreatment of the tissue with 2OHE2 prevented the augmented aortic contraction to (-)-adrenaline usually seen after inhibition of COMT. The non-additive nature of the sensitization seen after combined treatment with 2OHE2 and U-0521 was qualitatively similar to that seen following combined exposure to maximally effective concentrations of U-0521 and an inhibitor of extraneuronal uptake (hydrocortisone 100 mumol/l). Oestradiol and 2MeOE2 reduced the formation of both the 3H-O-methylated, 3H-deaminated and the 3H-O-methylated deaminated metabolites of 3H-(-)-adrenaline (0.15 mumol/l) during exposure of the aorta to the tritiated catecholamine.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000077584:2-Methoxyestradiol; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D065098:Catechol O-Methyltransferase Inhibitors; D002395:Catecholamines / Q000494:pharmacology*; D004837:Epinephrine / Q000378:metabolism / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011427:Propiophenones / Q000494:pharmacology; D011817:Rabbits
chemical_list: D065098:Catechol O-Methyltransferase Inhibitors; D002395:Catecholamines; D004967:Estrogens; D011427:Propiophenones; D004958:Estradiol; C006104:U 0521; D000077584:2-Methoxyestradiol; C001390:2-hydroxyestradiol; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine