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In this study we explored the possible underlying mechanism(s) of the differential transport of unfertilized and fertilized ova in cycling and pregnant rats. The number of ova recovered from rat oviducts and uterus was not significantly different in estrus, metestrus and diestrus but dropped sharply at proestrus. When estrus rats were injected with indomethacin (10(-6)), a well known inhibitor of cyclooxygenase, delivered into both ovarian bursae, and sacrificed next day at metestrus, the number of ova in the oviduct was significantly smaller (p less than 0.025) than in controls at metestrus. On the other hand, when diestrus rats were injected with PGE1 (10(-6)) delivered into both ovarian bursae, and sacrificed next day at proestrus, no ova were found in the oviducts, and only a few of them were in the uterus. When fertilized ova were recovered from oviducts and uteri at day 4 of pregnancy (corresponding to proestrus of cycling rats) an average of 4 embryos were still found in the oviducts, proving a differential ovum transport between cycling and pregnant rats. In order to establish if there exists any ova or embryo releasing factor responsible for this difference, the prostaglandins released to the incubation medium by ovum or 3-day embryo were measured. Unfertilized ova produced significantly more PGE1 (p less than 0.05) than PGE2 or PGF2 alpha. The same pattern of PG production was observed with incubated embryos, but in this case the amount of PGE1 released was significantly higher (p less than 0.01) that the PGE1 released by unfertilized ova.(ABSTRACT TRUNCATED AT 250 WORDS)

The present study was performed in order to explore the influence of ova present within rat oviducts on: a) tubal spontaneous motility and b) oviduct prostaglandin production. It was found that the isometric developed tension (IDT) of tubes isolated from proestrous rats (preovulatory oviducts) was significantly higher (P less than 0.01) than the IDT of tubes from rats at estrus and at metestrus (postovulatory oviducts). After flushing the oviducts with KRB solution (i.e., after removing existing ova) the IDT of the oviducts obtained from estrous rats increased significantly (P less than 0.01), whereas the IDT of tubes isolated from proestrous rats (i.e., preparations without ova) was not modified. On the other hand, isolated tubes containing their corresponding ova released into the suspending solution significantly more PGE1 than PGE2 or PGF2 alpha (P less than 0.005). It was particularly interesting to find that after flushing the oviducts, tissue production of PGE1, PGE2 and PGF2 alpha was similar. Finally, when dose response curves for PGE1 and for PGE2 on the spontaneous contractions of oviducts isolated from rats at proestrus, estrus and metestrus were constructed, both PGs evoked an inhibitory inotropic action. The ED50 for PGE1 in tubes from estrous rats was significantly smaller (P less than 0.01) than that for metestrous animals but significantly greater (P less than 0.01) than that observed in oviducts from proestrous rats. The ED50 for PGE2 did not change in the different tested periods of the sex cycle. Results reported herein suggest the possibility that the ova present within rat oviducts, may influence their own transport along the tubes by modifying the amount of prostaglandins produced by the oviducts or via their own prostaglandin synthesis.

The purpose of the present study was to explore whether, the stimulating contractile action of angiotensin II (AII) or of angiotensin I (AI), in uterine strips isolated from rats, either spayed or spayed and injected with 17-beta estradiol, was somehow linked to tissue generated prostaglandins (PGs). Indomethacin (10(-6)M), shifted to the left the dose-response curve for AII in preparations from ovariectomized animals; augmenting both, the efficacy and the potency of the agonist. Dose-response curves for AII were also explored in the presence of subthreshold concentrations of several exogenous PGs. PGE2 (10(-9) M) completely abolished the influence of indomethacin on the curve for AII; PGD2 (10(-9) M) did not evoke effects and PGF2 alpha (10(-9) M) only altered the threshold dose, the rest of the curve remaining similar to that obtained with indomethacin alone. The cumulative dose-response curve for AI, in strips isolated from ovariectomized rats, was comparable to that for AII and, the presence of indomethacin, only reduced the concentration for the threshold action of AI, in comparison to controls. Captopril (100 ng/ml), shifted to the right the dose-response curve for AI and indomethacin failed to alter the effects of AI in the presence of captopril. In strips isolated from ovariectomized rats, injected with 17-beta estradiol, the low concentration points of the dose-response curve for AII were shifted to the left of those for the agonist in control preparations from spayed rats not treated with estradiol. Furthermore, indomethacin failed to alter the responses to AII in strips from spayed animals injected with 17-beta estradiol. The foregoing results document that an inhibitor of tissue PGs synthesis, namely indomethacin, is able to modify the dose-response curve for AII, rather than that for AI, in the uterus from ovariectomized rats, but not in preparations from spayed animals treated with estradiol. This, as well as the effect of a subthreshold dose of PGs, suggest that a minimum of PGE2 is required for the contractile influence of AII and not for that of AI. Moreover, the absence of estrogen dominance appears, as well, as a crucial factor for the action of AII.

The effects of exogenous histamine (H) on prostaglandin (PG) generation and release in uteri isolated from diestrous rats and the influences of H2-receptors blockers (cimetidine and metiamide) on the output of uterine PGs, were explored. Moreover, the action of H on the uterine 9-keto-reductase, was also studied. Histamine (10(-4) M) failed to alter the basal output of PGE1 but reduced significantly the generation and release of PGE2 and augmented the output of PGF2 alpha. On the other hand, cimetidine (10(-5) M) enhanced the basal release of PGE2 but had no action on the outputs of PGs E1 or F2 alpha. The enhancing effect of H on the production and release of PGF2 alpha was abolished in the presence of cimetidine. Also, the antagonist reversed the influence of H on the output of PGE2. Metiamide, another H2-receptor antagonist, did not alter the basal control generation and release of uterine PGs, but antagonized the augmenting influence of H on PGF2 alpha uterine output, as much as cimetidine did, and prevented the depressive action of H on the release of PGE2 from uteri. Histamine (10(-4) M) significantly stimulated uterine formation of cyclic-adenosine monophosphate, an action which was antagonized by the presence of cimetidine (10(-5) M), a blocker of H2 receptors. Also, histamine (10(-5) M) and dibutyrylcyclic-adenosine monophosphate (DB-cAMP) at 10(-3) M, enhanced significantly the formation 3H-PGF2 alpha from 3H-PGE2. Results presented herein demonstrate that H is able to diminish the generation of PGE2 in uteri from rats at diestrus augmenting the synthesis of PGF2 alpha, apparently via the activation of H2-receptors, enhancing adenylate-cyclase. These effects appear to increase uterine 9-keto-reductase activity which transforms PGE2 into PGF2 alpha. Relationships between the foregoing results and those evoked by estradiol, are also discussed.

Cumulative dose-response curves for histamine induced responses in mesometrial (ME) and antimesometrial (AME) regions of uterine horns isolated from rats at 7th, 16th and 22nd days of pregnancy, were constructed. Histamine inhibited, in dose-related fashion, the isometric developed tension in ME and AME strips obtained at the 7th day of pregnancy, an action antagonized by cimetidine (10(-4)-10(-5) M). On the contrary, at the 16th and 22nd days, histamine (10(-5)-10(-3) M), stimulated spontaneous contractions in the ME region but had no effect in the AME segment. Although histamine and SKF-71481-A2,aH1-receptor agonist, both at 10(-4) M, enhanced similarly ME inotropism at the 16th and at 22nd days of pregnancy, the positive contractile action of histamine was greater at the 16th than at the 22nd day. Moreover, cumulative dose-response curves for histamine and SKF-71481-A2 in the ME region of uteri isolated at the 16th day of gestation, showed that both agonists have approximately the same inotropic potency and efficacy. On the other hand, pyrilamine (at 10(-4) M, but not at 10(-5) M aH1-receptor antagonist, shifted to the right the dose-response curve for histamine in ME strips from uteri at the 16th day of pregnancy and attenuated significantly, the magnitude of the positive inotropism evoked by the amine. Similar findings were observed in the presence of chlorpheniramine (at 10(-6) M), another H1-receptor blocker. In addition, the positive uterine inotropism evoked by histamine in the ME region of preparations isolated at the 16th day of pregnancy, was significantly reduced by an antagonist of phospholipase A2 (mepacrine, 10(-4) M) as well as by acetylsalicylic acid (ASA at 10(-4) M), an inhibitor of cyclooxygenase. Results also indicate that the excitatory uterine inotropism elicited by the agonistic amine in ME strips isolated from rats at the 16th day of pregnancy, was coincident with an enhanced release of prostaglandins (PGs) E2 and F2 alpha, but not of PGE1 and that both augmenting actions of histamine were antagonized by histamine H1 receptor-blockers, namely pyrilamine (mepyramine or chlorpheniramine. Results suggest that histamine at early pregnancy diminished myometrial inotropism via its interaction with H2-receptors, whereas from mid pregnancy up to the moment of parturition it evokes contractile stimulation, most likely due to the activation of H1-receptor located at the mesometrial region of rat uterine horns.(ABSTRACT TRUNCATED AT 400 WORDS)

The output of prostaglandins (PGs) E1, E2 and F2 alpha, from ampullary and isthmic portions of sow oviducts isolated during proestrus, estrus and metestrus, was explored. Moreover, in vitro cumulative dose-response curves for the contractile effect of these three PGs, on identical oviductal segments, were constructed. Isthmic preparations from proestrous and metestrous animals released more PGE1 and PGF2 alpha than PGE2 "like material". During estrus, the outputs of PGE1, PGE2 and PGF2 alpha were similar, whereas, oviducts from proestrous and metestrous sows released less PGE1 and PGF2 alpha than during estrus. Although the output of PGE2 "like material" from isthmic and ampullary segments did not differ significantly during the three stages of the sex cycle, ampullary metestrous preparations released more PGE1 and PGF2 alpha, than estrous or proestrous ones. The addition of PGE1, PGE2 or PGF2 alpha, consistently stimulated the amplitude of contractions of isthmic oviductal segments isolated from proestrous and metestrous sows. Within the concentration-range explored, dose-response curves for PGE2 and PGE1 were to the left of those for PGF2 alpha in the isthmus obtained before ovulation (proestrus) but not in segments isolated at later times (2-3 days) of the cycle (metestrus). The stimulatory dose-response curves for PGE1, or PGE2, in isthmic segments of metestrous preparations incubated with phentolamine (10(-6)M) were shifted to the right of controls not exposed to the adrenoreceptor blocker, whereas, the curve for PGF2 alpha without phentolamine, was identical to that obtained in its presence. PGE1 and PGE2 did not evoke significant contractile effects on oviductal ampullary portions from proestrous sows, whereas, PGF2 alpha was clearly stimulatory at concentrations of 10(-9)M and higher. In ampullary segments isolated after ovulation (metestrus) the threshold for contractile enhancement following PGF2 alpha was greater than during proestrus, whereas, PGE1 elicited a significant inhibition of contractions. The spontaneous contractile pattern exhibited by isthmic and ampullary oviductal regions, prior to and after ovulation, is discussed in terms of tissue PG generation and output and is compared with results regarding tubal motility following the exposure to exogenous PGs.