Prostaglandins and ovarian factors as modulators of the negative inotropic action of histamine in the isolated rat uterus

The present study reports findings on: a) the action of histamine (H) on the spontaneous motility of the uterus isolated from rats during four different stages of the sex cycle; b) the relevance of endogenous and exogenous prostaglandins (PGs) for the inotropic effect of H and c) the relationships between these factors and the generation and release of PGs in rat uterine horns obtained during proestrus, estrus, metestrus and diestrus. Cumulative done-response curves for H, in strips isolated from proestrous rats, showed that the agonist inhibited, at all the concentrations tested, spontaneous myometrial contractions, evoking a maximum effect (100% inhibition) at 10^-5M. Incubation with acetylsalicylic acid (ASA; 10^-4M) did not modify the dose-response curve for H. In strips from estrous rats, the maximum effect of H was obtained at 10^-3M and, after incubating with ASA, the control dose-response curve for H was shifted to the left. A subthreshold dose of PGE₂ (10-9M), reversed completely the action of ASA on H uterine responses, whereas PGF_2α was not effective. Dose-response curves for H, in uterine strips isolated from metestrous rats, showed the maximum effect (85% of inhibition) at 10^-3M. Incubation with ASA, shifted the curve to the left and, the maximum effect increased up to 100% inhibition. A subthreshold dose (10^-9M) of PGE₂ or of PGF_2α shifted to the right the dose-response curve for the amine. In uterine strips isolated from diestrous rats the maximum inotropic action of H evoked only 75% of contractile inhibition and, in the presence the ASA, this influence reached 100%; the dose-response for the agonist being shifted to the left. Both PGE₂ or PGF_2α, added in the presence of ASA, abolished the displacement evoked by ASA on the control dose-response curve for H. A significant correlation between the tissue output of "PGE-like material" into the bathing solution and the ED50 for the contractile influence of H, was also detected. On the contrary the release of "PGF_2α-like material" did not correlate with the ED₅₀ for H. The foregoing results suggest that some endogenous uterine prostaglandins of the 2 series, modulate the depressive inotropic action of H in isolated uterine strips, depending on the ovarian hormonal status of the animals.