Uterine catecholamines and prostaglandins during the estrous cycle of the rat.

The uterine contents of norepinephrine, epinephrine, dopamine, and prostaglandins F and E were determined on each day of the rat estrous cycle. Catecholamines were determined by high performance liquid chromatography with electrochemical detection (HPLC-EC) as well as by a radioenzymatic technique; prostaglandins were quantitated by RIA. The norepinephrine and dopamine values obtained by the radioenzymatic assay were approximately 1.5 times as high as the values obtained by HPLC-EC (norepinephrine, 285 vs. 188 ng/g; dopamine, 11.0 vs. 7.5 ng/g). Despite this difference in levels, both analytic techniques showed a decline in uterine norepinephrine from diestrus to estrus, followed by a significant (P less than 0.01) increase in norepinephrine on the day of metestrus. A cyclic pattern was also revealed for uterine dopamine concentration. There was a decline in dopamine concentration from diestrus to proestrus (radioenzymatic, P less than 0.01), followed by a return to high levels at metestrus (HPLC-EC). Epinephrine levels were low (undetectable by radioenzymatic assay; 24 ng/g by HPLC-EC) and showed no variation during the estrous cycle. Prostaglandin F was uniformly higher than prostaglandin E (10 vs. 2.5 ng/uterus). Significant increases in the uterine contents of both prostaglandins were shown on the day of proestrus.

Plasma prostaglandins in pregnancy.

Plasma prostaglandins were determined by radioimmunoassay in 92 pregnant and 14 nonpregnant women. There was significant elevation of PGA-like material in the first trimester of pregnancy (1744 pg/ml) over that seen in nonpregnant women (576 pg/ml) with continuation of that elevation in the second and third trimesters. No significant difference existed among PGE levels of the nonpregnant group (251 pg/ml) and the first two trimesters of pregnancy (384 pg/ml and 294 pg/ml); the PGE level of the third trimester group (443 pg/ml) was significantly elevated over that of the nonpregnant group. PGF levels remained constant during all trimesters (135 pg/ml, 144 pg/ml, and 130 pg/ml) but exhibited plasma concentrations significantly higher than the nonpregnant group (78 pg/ml). Potential role (s) of prostaglandins as mediators of cardiovascular and renal changes of pregnancy are discussed.

Plasma prostaglandins in the normal menstrual cycle.

Plasma prostaglandins were studied by radioimmunoassay on alternate days during the menstrual cycle in fourteen normal women. No cyclic patterns were found for A-like prostaglandins using an assay which measured 13,14-dihydro-PGA. Mean subject values of PGA-like prostaglandin ranged from 367 to 904 pg/ml and varied significantly among women. Prostaglandin E determinations showed an upward trend beginning 8 days before the LH peak. PGE subject means varied significantly and ranged from 182 to 362 pg/ml. Prostaglandin F did not exhibit a cyclic pattern. The average concentration of PGF for individual women ranged from 58 to 153 pg/ml, showing significant variance. The physiologic implications of the results are discussed as well as recommendations for the design of future studies.

Neuropeptide changes in compressed spinal nerve roots.

STUDY DESIGN: Compression-induced changes in the concentration of substance P and VIP (vasoactive intestinal polypeptide), in spinal nerve roots and dorsal root ganglia were studied in an experimental nerve root compression model in pigs. OBJECTIVES: To analyze by radioimmunoassay the concentration of the neuropeptides substance P and VIP in a model for experimental chronic nerve root compression. SUMMARY OF BACKGROUND DATA: Neuropeptides such as substance P and VIP seem to be involved in the transmission of pain and changes in the levels of these neuropeptides have been described in models where peripheral or spinal nerve injury was induced. METHODS: An ameroid constrictor was applied on a spinal nerve root just cranial to the dorsal root ganglion. The inner diameter of this constrictor is gradually reduced. After 1 or 4 weeks, tissue samples were taken from the nerve root cranial to the constrictor and from the dorsal root ganglion for measurement of substance P and VIP concentrations. RESULTS: There was a statistically significant increase in substance P concentrations in the compressed dorsal root ganglia when compared to the noncompressed dorsal root ganglia at both 1 and 4 weeks. Substance P concentration was also significantly increased in the nerve root after 1 but not after 4 weeks. The VIP levels were not significantly changed in either tissue. CONCLUSIONS: The results of the study indicates an increase in substance P levels in the dorsal root ganglion (after 1 and 4 weeks) and in the nerve root (after 1 week) in a model for chronic nerve root compression in pigs. There were no significant differences in the VIP concentrations. The study thus indicates that changes in substance P are related to experimental chronic nerve root compression.

Evaluation of biochemical and structural changes in individual porcine corpora lutea during prostaglandin F2 alpha-induced luteolysis with an in vivo implant system.

To date, no in vitro system has been devised to allow the study of both the functional and the structural regression of luteal cells in response to prostaglandin (PG) F2 alpha. This study describes the use of a novel intraluteal PGF2 alpha implant system that results in the death of individual corpora lutea (CL), while surrounding CL on the same ovary remain fully functional. By this technique, it was possible to study both the functional and the structural regression of individual CL in vivo, without the confounding effects resulting from the systemic injection of PGF2 alpha. Biochemical measurements of individual CL included progesterone concentration, protein kinase C activity, and diacylglycerol levels. Structural measurements included luteal weight and the protein:DNA ratio, which was used to estimate cell size. Further, the determination of large luteal cell size was accomplished directly via light microscopy. Nonpregnant gilts were injected with 5 mg of estradiol benzoate every 12 hr from 8:00 a.m. on Day 11 to 8:00 a.m. on Day 13 to prevent uterine PGF2 alpha secretion. At 7:00 a.m. on Day 13, CL on one ovary were selected at random to receive PGF2 alpha-implants (n = 4) or implant material only (n = 4), whereas the remaining CL on that ovary served as unimplanted controls. The other ovary was removed at the point, and the CL on that ovary served as 0-hr controls. Gilts were relaparotomized at 3, 6, 12, and 24 hr after CL implantation, the PGF2 alpha-implanted ovary was removed, and individual CL were evaluated. PGF2 alpha-implanted CL exhibited a decline (P < 0.05) in progesterone concentrations at 12 and 24 hr and a decline (P < 0.05) in weight at 24 hr when compared with control CL (implant-only, unimplanted, and 0-hr control CL). Furthermore, the protein:DNA ratio was reduced (P < 0.10) in the PGF2 alpha-treated CL at 12 and 24 hr. Moreover, this change in the protein:DNA ratio (cell size) was consistent with the reduced diameter (P < 0.05) of the large luteal cell in the PGF2 alpha-treated CL. Protein kinase C activity and diacylglycerol concentrations did not change (P > 0.10) and therefore appear to be unassociated with either functional or structural changes in the PGF2 alpha-treated CL. Contrary to in vitro culture studies, the results of our in vivo study demonstrate no clear role for protein kinase C in the PGF2 alpha-induced luteolytic process.(ABSTRACT TRUNCATED AT 400 WORDS)

Structural and mechanical changes of uterine arteries during pregnancy in the pig.

A dramatic 15-fold increase in uterine blood flow in pigs occurs during pregnancy in association with marked increases in uterine arterial (UA) diameter. This study was conducted to determine UA collagen and elastin content, diameter, alpha 1- and alpha 2-adrenergic receptor (AR) numbers, norepinephrine (NE) and in vitro reactivity to phenylephrine on d 0, 20, 50, 80 and 110 of pregnancy in the pig. Uterine arterial collagen content declined progressively throughout pregnancy (P less than .01), whereas the content of elastin remained constant from d 0 to d 80, then increased (P less than .05) from d 80 to d 110. The UA collagen to elastin ratio was correlated with UA diameter (r = -.69; P less than .01), which increased from 4.5 mm on d 0 to 9.0 mm on d 110. Uterine arterial alpha 1-AR numbers remained low and constant throughout pregnancy, consistent with its retained ability to contract in response to phenylephrine. Uterine arterial NE content declined (P less than .05) from d 20 to d 80 before increasing slightly to d 110. Uterine arterial alpha 2-AR numbers remained high from d 0 to d 80 before decreasing (P less than .05) to low values on d 110. These data are consistent with a reduced adrenergic neuronal control and increased elasticity of the UA during pregnancy in the pig.

Local and systemic effects of intrauterine estradiol-17 beta on luteal function of nonpregnant sows.

This study was conducted to determine if intrauterine injections of estradiol-17 beta (E2 beta) could maintain luteal function in nonpregnant sows. Eight sows were assigned to surgery on d 8 or 9 of the estrous cycle (first day of estrus = d 0). At surgery, cannulas were inserted bilaterally into the uterine artery (UA) and common utero-ovarian vein (UOV), as well as into the lumen of each isolated uterine horn. Electromagnetic blood flow transducers were placed around the middle uterine artery supplying each horn of four sows. After surgery, sows were assigned randomly to receive either intrauterine injections of vehicle (.9% NaCl) into both uterine horns (control sows) or E2 beta into one uterine horn (375 ng/injection) and vehicle into the other (treated sows) every 6 h from 1200 h on d 11 to 1200 h on d 15. Uterine blood flow (UBF) was quantified, and blood was sampled from the UA and UOV, periodically, from d 11 to 18. On d 18, sows were ovariectomized and corpora lutea (CL) were weighed. Blood plasma was subsequently analyzed for progesterone (P4) and prostaglandin F (PGF) by radioimmunoassay. Control sows had smaller (P less than .05) CL than treated sows on d 18 (3,046 +/- 614 vs 4,451 +/- 324 mg). Progesterone concentrations in UOV blood of treated sows tended to increase from d 11 (469 +/- 110 ng/ml) to 18 (626 +/- 209 ng/ml) while P4 in UOV blood of control sows decreased markedly (P less than .01) from d 11 (579 +/- 79 ng/ml) to 18 (14 +/- 5 ng/ml). In addition, UOV P4 concentrations on the E2-beta-injected side of treated sows were higher (P less than .05) than those on the vehicle-injected side from d 14 to 18. The UBF of two treated sows increased eightfold to 10-fold within 12 h of the first E2 beta injection and remained elevated through d 17, while UBF of two control sows remained constant. Prostaglandin F concentrations in UOV blood of treated sows were lower (P less than .05) than in UOV blood of control sows on d 14 and 15. There was no effect of side of E2 beta injection on PGF concentrations, which were similar in UOV blood draining both uterine horns of treated sows. Thus, the local effect of E2 beta in stimulating P4 secretion by the ipsilateral ovary is not due to reduced PGF concentrations in UOV blood draining the E2 beta-injected horn.

Changing adrenergic sensitivity of the caruncular arterial vasculature supplying the bovine placentome.

With the advancement of gestation, blood flow increases preferentially to the caruncular bed of the gravid uterus in association with a decreasing sensitivity of the uterus to the vasoconstrictive effects of circulating catecholamines. This study directly compared the sensitivity of the caruncular artery (CA) of the isolated bovine placentome to phenylephrine (PE), a specific alpha 1-adrenergic receptor (AR) agonist, with that to norepinephrine (NE) and epinephrine (E), both of which are alpha 1-, alpha 2-, and beta-AR agonists, at two stages of gestation (140 to 170 d, mid-pregnant; 210 to 270 d, late pregnant). The CA of each placentome was perfused with oxygenated Krebs Ringer solution into which PE, NE or E were administered; increases in intra-arterial pressure were recorded. Further, NE content and numbers of alpha 1- and alpha 2-AR in the CA, intercaruncular arteries (ICA) and uterine arteries (UA) were quantitated. The CA from mid-pregnant cows exhibited greater (P less than .05) contractile responses to NE and E than did the CA from late pregnant cows, whereas responsiveness to PE remained constant. No difference in NE content, alpha 1-AR or alpha 2-AR numbers were observed in the UA, ICA or CA between mid-pregnant or late pregnant cows. Alpha 1-AR numbers were similar in CA, ICA and UA. However, CA contained threefold greater alpha 2-AR numbers than either the ICA or UA (50.2 +/- 6.1 vs 14.6 +/- 1.6 and 14.8 +/- 2.4 fmol/mg protein, respectively; P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Abortifacient effects of a unique class of vasoactive lipids from Pinus ponderosa needles.

Pinus ponderosa needle (PN) ingestion by late pregnant cows results in decreased uterine blood flow, premature parturition, and retained placentae. Further, plasma from PN-fed cows increases caruncular arterial tone (i.e., induces prolonged contraction) in an isolated perfused bovine placentome. A novel class of vasoactive lipids was isolated and identified using a bovine placentome assay-guided fractionation of CH2Cl2 extracts of PN. Placentome perfusion tests indicated that 1-12-dodecanedioyl-dimyristate (14-12-14) was the most potent of the PN lipids for increasing caruncular arterial tone. Late pregnant guinea pigs (GP) were used to evaluate the abortifacient activity of these vasoactive lipids. In Study 1, on d 50 of gestation, part of the control diet was replaced with chopped PN (Diet A) or chopped PN subjected to sequential extraction with diethyl ether (Et2O; Diet B); Et2O and CH2Cl2 (Diet C); and Et2O, CH2Cl2, and methanol (Diet D). The GP on Diets A and B exhibited shorter (P<.01) gestation lengths and reduced (P<.01) pig birth weights than GP on the control diet or Diets C and D. Further, only GP on Diets A and B exhibited retained placentae. In Study 2, on d 50 of gestation, part of the control diet was replaced with chopped PN that had been subjected to exhaustive CH2Cl2 extraction and then infiltrated with either CH2Cl2 alone (Diet E), CH2Cl2 containing 14-12-14 (Diet F), or CH2Cl2 containing isocupressic acid (Diet G); then solvents were evaporated. The GP consuming Diet F had shorter (P<.05) gestation lengths and reduced (P<.05) pig birth weights than did GP consuming Diets E or G. The GP consuming Diet F also exhibited a high incidence of retained placentae. These data provide evidence that a unique class of vasoactive lipids in PN exhibit abortifacient activity in guinea pigs.

Evidence for declining extracellular calcium uptake and protein kinase C activity in uterine arterial smooth muscle during gestation in gilts.

Uterine arterial blood flow and uterine arterial diameter are known to increase dramatically and progressively throughout gestation. Previous data from our laboratory have demonstrated that the KCl-induced membrane depolarization of uterine arterial smooth muscle specifically induces Ca2+ uptake through the potentially sensitive channels (PSC). Evidence from other laboratories suggests that calcium uptake through the PSC mediates long-term changes in uterine arterial diameter and flow (tone), possibly through activation of protein kinase C (PKC). In study 1 we evaluated uterine arteries removed from gilts on Days 20, 50, 80, and 110 of gestation for their ability to take up extracellular Ca2+ and to contract in response to a depolarizing dose of KCl. The ability of KCl to induce contraction of uterine arteries as well as its ability to stimulate extracellular 45Ca2+ uptake by these same arteries declines (p less than 0.01) progressively from Day 20 through Day 110 of gestation. Estrogen concentrations in systemic blood were negatively correlated with the contractile response (r = -0.57; p less than 0.01) and extracellular 45Ca2+ uptake (r = -0.93; p less than 0.0001) of uterine arteries during gestation. In study 2 we evaluated changes in uterine arterial PKC and protein kinase M (PKM) throughout the estrous cycle and gestation. It was determined that cytosolic PKC declined with the advancement of gestation whereas PKM progressively increased (r = -0.63; p less than 0.01). These data suggest a decreasing ability of the uterine artery to take up extracellular Ca2+ through the PSC as gestation advances, in association with decreasing cytosolic PKC.

Increase in uterine peroxidase activity in the rat uterus during oestrogen hyperaemia.

The administration of oestrogen results in increased arterial blood flow in all mammalian species studied to date, but its mechanism of action has not been elucidated. Because an interval of 30-60 min is observed between oestrogen injection and uterine hyperaemia, it has been suggested that a vasoactive intermediate is involved and recent evidence suggests that catechol oestrogens are the vasoactive oestrogen intermediates. Uterine peroxidase catalyses the conversion of oestrogens to their catechol forms and thus may play an important role in oestrogen-induced uterine hyperaemia. The present studies evaluated the time course and dose-response effects of oestrogen on uterine peroxidase activity and related these to changes in uterine blood volume, an index of uterine hyperaemia in immature rats. These data demonstrated that the minimal effective hyperaemic dose of oestradiol also increased (P less than 0.05) uterine peroxidase activity. The oestradiol-induced increase in uterine peroxidase activity preceded significant increases in uterine blood volume (1 h versus 2 h, respectively). These data are consistent with a role for peroxidase-mediated conversion of oestradiol to catechol oestradiol in facilitating uterine hyperaemia in rats.

Effect of prostacyclin inhibition by tranylcypromine on uterine 6-keto-pgf 1 alpha levels during estrogen hyperemia in rats.

A role for prostacyclin (PGI2) as a mediator of estrogen-induced increases in uterine blood volume (UBV) was investigated by measuring uterine tissue levels of 6-keto-prostaglandin F1 alpha (6-keto-PGF 1 alpha), and testing estrogen responses in rats pretreated with the PGI2 synthesis inhibitor, tranylcypromine (TCP). Uterine 6-keto-PGF1 alpha content was determined by radioimmunoassay of tissue extracts purified through the use of high-performance liquid chromatography (HPLC). Estrogen treatment of castrate rats resulted in a significant increase of uterine 6-keto-PGF 1 alpha was compared to saline treated controls (9.3 ng/uterine horn vs 6.7 ng/uterine horn, p=0.01). Pretreatment with TCP (20 mg/kg) markedly reduced the uterine content of 6-keto-PGF 1 alpha (2.5 ng/uterine horn). The typical 50% increase in UBV observed after estrogen was unaffected by tranylcypromine pretreatment. It was concluded that the increased PGI2 synthesis, as indicated by elevated levels of 6-keto-PGF1 alpha, may function as an amplifying mechanism for the uterine vasodilation-induced by estrogen in castrate rats, but that production of this prostanoid is not essential for the estrogen response.

Prostaglandin F2 radioimmunoassay utilizing polyethylene glycol separation technique.

PIP: A radioimmunoassay for Prostaglandin F which utilizes polyethylene glycol to separate antibody-bound and free prostaglandin is discribed. The detailed procedure for extraction and chromatographic fractionalization of the "E" and "F" series is presented. The recoveries of labeled prostaglandin obtained at each step of the procedure compared favorably with the 68% overall recovery figure for the complete assay. Data on the sensitivity, specificity, accuracy and reproducibility of the assay are presented. PgF levels in plasmas obtained from normal males and females, pregnant females in the third trimester and females in labor have been determined. Ovarian and uterine tissue levels of Prostaglandin F are also included.^ieng

Effects of ingestion of pine needles (Pinus ponderosa) by late-pregnant beef cows on potential sensitive Ca2+ channel activity of caruncular arteries.

Cows were fed either a control (n = 6) or pine needle (n = 12) diet beginning on day 249 of pregnancy. On day 3 and day 5 of feeding, control-fed and pine needle-fed cows were slaughtered and placentomes were collected for in vitro perfusion of the caruncular artery. Potential sensitive Ca2+ channel (PSC) activity as well as the responsiveness to phenylephrine (alpha 1-adrenergic agonist) and adrenaline (alpha 1- and alpha 2-adrenergic agonist) were determined. Selected gravid uterine tissues (endometrium and myometrium, as well as caruncular and cotyledonary tissues) and associated arteries (caruncular, intercaruncular and umbilical) were isolated, minced and portions either extracted immediately for measurement of PSC or frozen at -90 degrees C until assayed for peroxidase activity or number of alpha 2-adrenergic receptors and affinities or for both. In vitro perfused placentomes from day 5 pine needle-fed cows had greater (P < 0.05) PSC activity, as measured by the increase in perfusion pressure in response to a depolarizing dose of KCl, than day 3 pine needle-fed or control-fed cows (10.3 +/- 2.5 versus 6.1 +/- 1.2, and 4.3 +/- 0.7 kPa, respectively). Furthermore, day 5 pine needle-fed cows also exhibited greater (P < 0.05) contractile responses to adrenaline than day 3 pine needle-fed or control-fed cows. Contractile responses to phenylephrine were similar (P > 0.1) for all three treatment groups. The observed increase in PSC activity and responsiveness to adrenaline, however, was not reflected by increasing numbers or affinities of PSC or alpha 2-adrenergic receptors on caruncular arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of parasympathetic decentralization and paracervical ganglion excision on reproductive function in the rat.

The uterine paracervical ganglion (Frankenhauser's ganglion) contains the terminal ganglion cells of the sacral parasympathetic system and, in some species, the short adrenergic system. Histochemical studies also show numerous chromaffin cells with morphologic attributes of interneurons. The present study explores the function of cell types present in this ganglion, by seeking changes in reproductive function following either parasympathetic decentralization (transection of the cauda equina) or excision of the ganglion itself. Two well-known reproductive phenomena were observed after each surgical intervention, namely, induction of uterine hyperemia by estrogen administration, and maintenance of normal vaginal cycles. Estrogen-induced uterine hyperemia was not affected by parasympathetic decentralization or ganglion excision. Therefore, nerves originating in, or passing through this structure may be eliminated as components of the vascular control mechanism. In contrast, compared to sham-operated controls, ganglionectomy caused a significant reduction in the proportion of animals exhibiting normal vaginal cycles postoperatively (P less than 0.05). Cycle distribution was more evident in animals ganglionectomized on metestrus (P less than 0.01) and proestrus (P less than 0.05) than in animals ganglionectomized on diestrus or estrus. Since parasympathetic decentralization did not produce cycle disruption similar to ganglionectomy, one may conclude that the cycle-modulating effect does not involve preganglionic fibers of the sacral parasympathetic nerves.

Electron microscopic and histochemical characterization of intra-arterial cushions of the rat and porcine uterine vascular bed.

Scanning and transmission electron microscopic studies, together with histochemical investigations, were conducted on rat and porcine intra-arterial cushions from the uterine vascular bed. In the rat, the fine structure of these cushions closely resembled that previously described in the rat kidney. The cushions were composed of modified smooth muscle, circularly disposed in an incomplete, raised band surrounding the entrance to arterial branches. These muscle cells projected as attenuated processes throughout the loosely organized, PAS-positive stroma, and established close contact with thin endothelial extensions projecting from the base of the surface endothelial cells. Scanning electron microscopic observations of furrows on the endothelial surface gave rise to the suggestion that such contacts might mediate muscular control of endothelial surface topology. In similar cushions from the pig uterine artery, the smooth muscle of the cushions was much more compactly organized, and was disposed radially, rather than circumferentially, within the cushion structure. The enzyme histochemical profile of porcine cushions did not differ appreciably from that of normal vascular smooth muscle and endothelium, suggesting the maintenance of a metabolic similarity with adjacent tissues. These studies clarify the fine-structural basis for recently reported contraction and relaxation of uterine artery cushions during ischemia and perfusion of the rat uterine vascular bed, and thus, for their functional role in the regulation of uterine vascular flow.

Radioimmunoassay of PGE and an approach to the specific measurement of PGE1.

A specific radioimmunoassay for prostaglandins of the E series is presented. Several refinements of the conventional procedures used for unknown sample preparation prior to assay are described. Validation of the method through recovery of labeled and unlabeled prostaglandin E from plasma indicates: 74% extraction efficiency, 80% chromatographic separation efficiency, and a 67% overall recovery figure for the complete assay. The development of an "absorbed system" approach for measuring one E prostaglandin (PGE1) without interference from the other E prostaglandin (PGE2) is also described. A preliminary study of rat tissue and male plasma samples measured by these assay systems is included. Alternate approaches to the development of a specific PGE1 assay, although less feasible in these authors' hands, are discussed.

A technique for monitoring blood flow changes with miniaturized Doppler flow probes.

A method for constructing miniaturized Doppler blood flow probes is presented. Since these probes weigh less than 100 mg and have crystal heads less than 0.5 mm in size, they are suitable for chronic placement on vessels as small as 200 micron. The probes are positioned under the vessel and rotated to optimize the Doppler signal. While held in that position, the crystal head is attached to the adventitia of the vessel with cyanoacrylate glue. A cuff holding the vessel and probe in the chosen position is then formed in situ by the application of a drop of silicone polymer. Data are presented showing the linearity of a flow probe response with the volume blood flow at rates as low as 14 microliter/min. With the use of the uterine artery of the conscious, unrestrained rat as an example, the probe was demonstrated to detect a dynamic change in flow.

Role of endogenous prostaglandins in regulation of uterine blood flow and adrenergic neurotransmission.

Earlier studies from these laboratories have demonstrated that prostaglandins (PG's) of the A and E series are potent uterine vasodilators whereas PGF's do not significantly alter uterine vascular resistance. In addition, PGE's and PGF's are also able to modify adrenergic vasoconstrictor responses in the canine uterus. In the present study the role of endogenous prostaglandins in regulating uterine vascular resistance and adrenergic neurotransmission was evaluated. Intra-arterial infusion of the prostaglandin synthesis inhibitor meclofenamate resulted in a significant reduction in PGE levels in uterine venous plasma and increased vascular resistance. Uterine vasoconstrictor responses produced by sympathetic nerve stimulation and norepinephrine were enhanced when endogenous PG synthesis was inhibited. During sympathetic nerve stimulation, uterine venous plasma levels of radioimmunoassayable prostaglandins of the E of F series did not change, suggesting that the adrenergic activation of PG synthesis is not detectable in uterine venous efferent. These data suggest that endogenous prostaglandins of the E series appear to play an important role in regulating uterine blood flow (I) by relaxing uterine vascular smooth muscle and (2) by depressing adrenergic vasoconstrictor responses.

Luteal maintenance during early pregnancy in the pig: role for prostaglandin E2.

We previously demonstrated that prostaglandin E2 (PGE) directly inhibits prostaglandin F2 alpha (PGF)-induced regression of individual pig corpora lutea (CL) in a dose dependent manner. The present experiments were conducted to 1) characterize and compare uterine secretion of PGE and PGF during the estrous cycle and early pregnancy and 2) evaluate the local effect of the conceptus on uterine prostaglandin secretion and associated CL function in unilaterally pregnant pigs. In Experiment 1, utero-ovarian venous blood samples were collected from two nonpregnant and two pregnant gilts at 3-h intervals from day 10 through 16 (first day of estrus or mating = day 0) for quantitation of uterine PGE and PGF secretion. In Experiment 2, gilts (n = 4) were made unilaterally pregnant on day 2, and utero-ovarian venous catheters were placed bilaterally to determine if differences in PGE and/or PGF secretion might account for the known luteotrophic/antiluteolytic effect of the gravid uterine horn on the CL of the ipsilateral ovary. During the estrous cycle (Experiment 1), pulsatile secretion of PGF increased markedly on day 13 and continued to increase through day 16. PGE secretion also increased from day 13 to 16 of the estrous cycle; however, concentrations of PGE remained at least 3-fold lower than those of PGF. In contrast to changes in non-mated gilts, prostaglandin secretion in mated gilts peaked earlier (day 11-12), with PGE predominating. Thereafter, both PGE and PGF secretion declined to basal levels where they remained through day 16 of pregnancy. During unilateral pregnancy (Experiment 2), PGF concentration in nongravid and gravid horns was similar (P > 0.8). In contrast, PGE concentrations were greater (P < 0.06) in utero-ovarian venous blood draining the gravid uterine horn. This increase in PGE was associated with enhanced CL function on the ipsilateral ovary as evidenced by an elevated progesterone content and concentration as well as increased CL weights. These data are consistent with a role for conceptus-associated increases in uterine PGE secretion in the local stimulation of luteal function during early pregnancy in the pig.