Inhibitory effects of some catecholamines on contractions of uterine strips isolated from estrous and spayed rats. Influence of endogenous and exogenous prostaglandins on the action of methoxamine.

Cumulative dose-response curves were produced for the effect of different adrenergic agonists on the contractions of uterine strips from natural estrous and ovariectomized rats. Isoproterenol, norepinephrine and phenylephrine inhibited uterine spontaneous contractions, whilst methoxamine stimulated them. The inhibitory influences were blocked by propranolol and the excitatory effect of methoxamine was abolished by phentolamine. However, the sensitivity of the rat uterus to beta- and alpha-adrenergic agonists varied depending on the hormonal state i.e. strips from rats in natural estrus were more sensitive to inhibitory effect of beta-agonist than were those from ovariectomized animals. On the contrary, the apparent potency and the efficacy of an alpha-agonist (methoxamine) was higher in ovariectomized uterine strips than in those from estrous rats. Indomethacin, at a concentration known to inhibit the endogenous synthesis of prostaglandins, depressed the spontaneous activity of strips from spayed rats and prevented the response to methoxamine, whereas in strips from natural estrous rats, the drug was unable to modify either the spontaneous contractions or the stimulating action of methoxamine. In addition in the presence of threshold doses of PGE1, PGE2 and F2 alpha the dose-response curve to methoxamine shifted to the left for uterus from ovariectomized animals. The results suggest that uterine strips from estrous rats have more affinity to the effect of beta-adrenergic agonists, whereas those from spayed animals were more sensitive to the effect of an alpha-adrenergic agent. Also the effectiveness of an alpha-adrenergic agonist, methoxamine, appears to be related to unaltered tissue prostaglandins.