Infusion Of Prostaglandin F2 Alpha Research Articles

Patterns of Gene Expression in the Bovine Corpus Luteum Following Repeated Intrauterine Infusions of Low Doses of Prostaglandin F2alpha1

Natural luteolysis involves multiple pulses of prostaglandin F2alpha (PGF) released by the nonpregnant uterus. This study investigated expression of 18 genes from five distinct pathways, following multiple low-dose pulses of PGF. Cows on Day 9 of the estrous cycle received four intrauterine infusions of 0.25 ml of phosphate-buffered saline (PBS) or PGF (0.5 mg of PGF in 0.25 ml of PBS) at 6-h intervals. A luteal biopsy sample was collected 30 min after each PBS or PGF infusion. There were four treatment groups: Control (n = 5; 4 PBS infusions), 4XPGF (4 PGF infusions; n = 5), 2XPGF-non-regressed (2 PGF infusions; n = 5; PGF-PBS-PGF-PBS; no regression after treatments), and 2XPGF-regressed (PGF-PBS-PGF-PBS; regression after treatments; n = 5). As expected, the first PGF pulse increased mRNA for the immediate early genes JUN, FOS, NR4A1, and EGR1 but unexpectedly also increased mRNA for steroidogenic (STAR) and angiogenic (VEGFA) pathways. The second PGF pulse induced immediate early genes and genes related to immune system activation (IL1B, FAS, FASLG, IL8). However, mRNA for VEGFA and STAR were decreased by the second PGF infusion. After the third and fourth PGF pulses, a distinctly luteolytic pattern of gene expression was evident, with inhibition of steroidogenic and angiogenic pathways, whereas, there was induction of pathways for immune system activation and production of PGF. The pattern of PGF-induced gene expression was similar in corpus luteum not destined for luteolysis (2X-non-regressed) after the first PGF pulse but was very distinct after the second PGF pulse. Thus, although the initial PGF pulse induced mRNA for many pathways, the second and later pulses of PGF appear to have set the distinct pattern of gene expression that result in luteolysis.

The effect of intrahypothalamic infusion of prostaglandin F2alpha on body temperature and behaviour in chicks.

Journal Article The effect of intrahypothalamic infusion of prostaglandin F2α on body temperature and behaviour in chicks Get access Jennifer E Whelan Jennifer E Whelan University Department of Pharmacology, Oxford University, South Parks Road, Oxford OX1 3QT, U.K. Search for other works by this author on: Oxford Academic Google Scholar Journal of Pharmacy and Pharmacology, Volume 28, Issue 6, June 1976, Page 536, https://doi.org/10.1111/j.2042-7158.1976.tb02788.x Published: 12 April 2011 Article history Received: 12 January 1976 Published: 12 April 2011

Progesterone responses to intravenous and intrauterine infusions of prostaglandin F2α in mares

The hypotheses were tested that prostaglandin F2alpha (PGF) travels from the uterus to the ovaries via a systemic route in mares, as opposed to a local route in ruminants, and that one pulse of PGF produces only partial luteolysis. Intravenous (i.v.) and intrauterine (i.u.) infusions of PGF were performed 8 days after ovulation at a constant rate for 2 h. Plasma concentrations of PGF were assessed by assay of 13,14-dihydro-15-keto-PGF2alpha (PGFM). Total doses administered were as follows: 0, 0.05, 0.1, 0.5 and 1.0 mg, i.v., PGF and 0 and 0.5 mg, i.u., PGF (n=4 mares per group). In addition, PGFM concentrations were determined for natural pulses from samples collected each hour during luteolysis (n=5). Progesterone was similarly reduced by 4 days after treatment in the 0.5 mg i.v., 0.5 mg i.u. and 0.0 mg i.u. groups. The area under the PGFM curve in the 0.1 mg i.v. group was similar to the area for natural PGFM pulses. Progesterone decreased to a similar concentration by 12 h in the 0.1, 0.5 and 1.0 mg i.v. groups, but thereafter was greater (P<0.05) in the 0.1 mg i.v. group. Progesterone concentrations reached <2 ng mL(-1) 6 days after treatment in the 0.05 and 0.1 mg i.v. groups and 2 days after treatment in the 0.5 and 1.0 mg i.v. groups. The results support the hypotheses of a systemic uteroluteal route for PGF transfer and that one pulse produces only partial luteolysis in mares.

IN VIVO CHANGES IN PROTEIN EXPRESSION OF THE GELATINASES, MATRIX METALLOPROTEINASES -2 AND -9 (MMP-2 AND MMP-9), AND TISSUE INHIBITORS OF METALLOPROTEINASES -1 (TIMP-1) IN THE OVINE CORPUS LUTEUM (CL) AFTER MULTIPLE PULSES OF PROSTAGLANDIN F2ALPHA (PGF2A)

A model was established in sheep which mimics the frequency of prostaglandin F2alpha (PGF2a) pulses during the course of natural luteolysis. Using this model, we previously demonstrated that after one and two pulses of PGF2a, protein mediators of the extracellular matrix (ECM), tissue inhibitors of matrix metalloproteinases (TIMPs) -1 and -2, decreased dramatically in luteal tissue within one hour following each PGF2a pulse, which was accompanied several hours later by an increase in matrix metalloproteinase-2 (MMP-2) activity. The objective of the present study was to study the temporal protein expression patterns of the gelatinases, matrix metalloproteinases (MMP) -2 and MMP-9, and TIMP-1, in corpora lutea of sheep which received three systemic pulses of PGF2a (20ug/min/1hr) during the mid-luteal phase of the cycle. Intact cycling ewes were given 2 injections (7.5 mg) of Lutalyse and housed with a vasectomized marker ram to detect estrus (day 0). Sheep were then housed in metabolism cages, and infused with PGF2a via the right jugular vein to mimic the endogenous uterine pulses during luteolysis. Corpora lutea (day 10–12; n=4 sheep for each time point) were removed surgically one hr (-1hr) before the third pulse of PGF2a and at 1, 8, 16, and 24 hrs after the third infusion of PGF2a. Gelatin zymographic analysis identified the presence of three bands with relative molecular masses of approximately 85, 70, and 64 kDa. These bands co-migrated with MMP-9 (85kDa) and MMP-2 (70 and 64 kDa) gelatinase family members present in the positive control, which was conditioned medium of the fibrosarcoma cell line, HT-1080. An analysis of variance followed by Tukey's revealed no differences in the expression of the 64 kDa MMP-2 species, but the expression of the 70 kDa MMP-2 species between the 16 and 24 hr time points differed significantly (p<0.05). In our previous studies with one or two pulses of PGF2a, no differences were observed for MMP-9. In the present study, after three pulses of PGF2a, expression of the 85 kDa MMP-9 species tended to increase (p= 0.07) at 16 hrs relative to the pre- infusion (-1hr) time point. A band of approximately 30 kDa, which comigrated with a TIMP-1 recombinant protein, was identified by immunoblot analysis. Although expression of TIMP-1 fluctuated greatly, the variation among samples for each time point negated any differences (p>0.05) in the temporal expression of this protein. In summary, the increase of the 70 kDa MMP-2 species accompanied by an increasing trend of the 85 kDa MMP-9 species and varying expressions of TIMP-1 indicate changes in protein mediators of the CL in response to the third pulse of PGF2a. These results, taken together with our previous findings, indicate a continuum of changes in protein regulators of the ECM within the CL as luteolysis progresses. (Supported by USDA Grant #2004-35203- 14176) (poster)

Intrauterine irrigation with prostaglandin F2‐α for management of severe postpartum hemorrhage

Severe postpartum hemorrhage is a significant contributor to maternal morbidity and mortality. The use of prostaglandin F2-alpha to control severe postpartum hemorrhage may avert surgery for the control of bleeding. After ruling out the possibility of genital tract injuries, 18 patients with severe postpartum hemorrhage caused by uterine atony were enrolled in the study. None of the patients responded to treatment with oxytocin, methylergonovine, or uterine massage. A Foley catheter was introduced into the uterine cavity and the balloon was inflated with 5 ml sterile saline solution. The catheter was connected to an infusion line of 500 ml saline solution containing 20 mg prostaglandin F2-alpha. The solution was infused at a rate of 3-4 ml/minute for the first 10 min, and then reduced to 1 ml/minute for a period of 12 24 hours. In 17 patients (94.4%) bleeding ceased within several minutes of initiation of intrauterine prostaglandin F2-alpha infusion, the uterus was firmly contracted and uterine bleeding did not recur. In one patient with placenta increta bleeding continued and hysterectomy was performed. None of the patients had any side effects. Intrauterine irrigation with low concentrations of prostaglandin F2-alpha is a simple, rapid and effective treatment for severe postpartum hemorrhage and facilitates constant and continuous hemostasis. Moreover, the minute dosage used eludes potentially complicating side effects.

Actions of magnesium, nifedipine and clonidine on the fetal vasculature of the human placenta.

The anticonvulsant magnesium and the antihypertensives clonidine and nifedipine are extensively used for the clinical treatment of preeclampsia and eclampsia. Little, however, is known about the possible effects of these agents on human fetal-placental vascular resistance. We therefore examined the actions of these agents on the human fetal placental vascular bed in vitro relating the concentrations causing any vasoactive effects to the maternal blood levels attained during treatment. Placentas (n = 24) were obtained within 20 minutes of delivery from women (aged 30.2 +/- 0.9 years). In each a placental lobule was bilaterally perfused with Krebs' solution (5 mL/minute, 37 degrees C, 95% O2, 5% CO2) and fetal arterial inflow pressure (FAP) monitored. Submaximal vasoconstriction of the fetal vascular bed was induced by continuous infusion of prostaglandin F2 alpha (4.2 +/- 0.5 microM) which increased FAP from 25.9 +/- 3.9 to 95.1 +/- 6.2 mm Hg. Using a group of placentas for each drug, the effects of MgCl2, nifedipine and clonidine, were examined. Magnesium (0.3-100 mM) (n = 4) dilated the placental fetal circulation with an IC50 of 8.1 mM and a maximal response of 89.7 +/- 3.6% (n = 4). This effect of Mg2+ was not changed during concomitant infusion of the cyclo-oxygenase inhibitor, indomethacin (3 microM). Nifedipine (3-10,000 nM) also produced vasodilatation (maximum response 42 +/- 9%, n = 5). Clonidine (3-1,000 nM) caused no significant change (p < 0.05 n = 5) in vascular resistance (maximum response 11.2-5.7%) relaxation), when compared to controls. Thus in concentrations likely to be therapeutically present in maternal blood, magnesium causes a greater degree of placental fetal vasodilatation than does nifedipine, whereas clonidine is unlikely to have any effect on fetal placental vascular resistance.

Inhibition by the protein kinase C activator 4 beta-phorbol 12-myristate 13-acetate of the prostaglandin F2 alpha-mediated and noradrenaline-mediated but not glucagon-mediated activation of glycogenolysis in rat liver.

In perfused rat livers, infusion of prostaglandin F2 alpha (PGF2 alpha) or noradrenaline increased glucose and lactate output and reduced flow. Glucagon increased glucose output and decreased lactate output without influence on flow. Infusion of phorbol 13-myristate 14-acetate (PMA) for 20 min prior to these stimuli strongly inhibited the metabolic and hemodynamic effects of noradrenaline, reduced the metabolic actions of PGF2 alpha but did not alter the effects of glucagon. In isolated rat hepatocytes PGF2 alpha, noradrenaline and glucagon activated glycogen phosphorylase but only PGF2 alpha and noradrenaline increased intracellular inositol 1,4,5-trisphosphate (InsP3). The noradrenaline- or PGF2 alpha-elicited activation of glycogen phosphorylase and increase in InsP3 were largely reduced after preincubation of the cells for 10 min with PMA, whereas the glucagon-mediated enzyme activation was not affected. In contrast to PMA, the phorbol ester 4 alpha-phorbol 13,14-didecanoate, which does not activate protein kinase C, did not attenuate the PGF2 alpha- and noradrenaline-elicited stimulation of glucose output, glycogen phosphorylase and InsP3 formation. Stimulation of InsP3 formation by AlF4-, which activates phospholipase C independently of the receptor, was not attenuated by prior incubation with PMA. Plasma membranes purified from isolated hepatocytes had both a high-capacity, low-affinity and a low-capacity, high-affinity binding site for PGF2 alpha. The Kd of the high-capacity, low-affinity binding site was close to the concentration of PGF2 alpha that increased glycogen phosphorylase activity half-maximally. Binding to the high-capacity, low-affinity binding site was enhanced by guanosine 5'-O-(3-thio)triphosphate (GTP[S]). This high-capacity, low-affinity site might thus represent the receptor. The Bmax and Kd of the high-capacity site, as well as the enhancement by GTP[S] of PGF2 alpha binding to this site, remained unaffected by PMA treatment. It is concluded that, in hepatocytes, activation of protein kinase C by PMA interrupted the InsP3-mediated signal pathway from PGF2 alpha via a PGF2 alpha receptor and phospholipase C to glycogen phosphorylase at a point distal of the receptor prior to phospholipase C.

Vascular actions of purines in the foetal circulation of the human placenta.

1. The vasoactive effects of adenosine triphosphate (ATP), adenosine and other purines in the foetal circulation of the human placenta were examined. Single lobules of the placenta were bilaterally perfused in vitro with Krebs buffer (maternal and foetal sides 5 ml min-1 each, 95% O2:5% CO2, 37 degrees C). Changes in foetal vascular tone were assessed by recording perfusion pressure during constant infusion of each purine. To allow recording of the vasodilator effects, submaximal vasoconstriction was induced by concomitant infusion of prostaglandin F2 alpha (0.7-2.0 mumol l-1). 2. ATP (1.0-100 mumol l-1) usually caused concentration-dependent reductions in perfusion pressure. However, biphasic with initial transient increases, or only increases in pressure were sometimes observed. Falls in pressure caused by ATP were significantly reduced by addition to the perfusate of NG-nitro-L-arginine (L-NOARG) (100 mumol l-1) but not NG-nitro-D-arginine (D-NOARG) (100 mumol l-1). They were not influenced by addition of indomethacin (10 mumol l-1) or L-arginine (100 mumol l-1). 3. Adenosine (0.01-1.0 mmol l-1) consistently caused concentration-dependent reductions in perfusion pressure, this effect not being influenced by indomethacin. L-NOARG, but not D-NOARG, reduced the potency of adenosine approximately three fold. L-Arginine, but not D-arginine enhanced its potency by a similar amount. 4. 2-Methylthio-ATP, a selective P2 gamma agonist was approximately 50 times more potent than ATP as a vasodilator agent, always causing decreases in perfusion pressure. 5. Beta-gamma-Methylene ATP, a selective P20 agonist, was approximately 100 times more potent than ATP as a vasoconstrictor, but only caused transient increases in perfusion pressure.6. The rank order of vasodilator potencies of a selection of adenosine receptor agonists was, 2-chloroadenosine>>5-(N-cyclopropyl)-carboxamidoadenosine, >5-N-ethylcarboxamidoadenosine, >2-chloro-N6-cyclopentyladenosine, >CGS-21680 > N6-cyclohexyladenosine = adenosine. Vasodilatation due to adenosine was inhibited by the PI-A2 receptor antagonist 3,7-dimethyl-l-propargylxanthine(DMPX).7. These results suggest that ATP may cause an endothelium-dependent vasodilatation in the foetal vessels of the human placenta via activation of a P2y receptor linked to the formation of nitric oxide(NO). Vasodilatation caused by ATP may mask an accompanying vasoconstrictor effect mediated, via a P2X receptor, in the villous vascular smooth muscle. Adenosine acting on P1-A2 receptors, which are also present in the foetal vasculature, may require synergistic interaction with NO to achieve a maximal vasodilator response.

RELEASE OF A SUBSTANCE FROM THE HUMAN PLACENTA HAVING DIGOXIN‐LIKE IMMUNOREACTIVITY

1. The human placental lobule, perfused with a constant flow (5 mL/min) of Krebs' solution after delivery at term, released into the fetal perfusate a digoxin-like substance, as measured by a fluorescence polarization immunoassay. 2. Initially the venous concentration was 360 +/- 66.7 pmol/L digoxin equivalents. This level did not change significantly during fetal vasoconstriction induced by prostaglandin F2 alpha infusion and persisted for the duration of the experiment (1.5-2 h). 3. Infusion into the fetal circulation of Fab fragments of sheep antibodies to digoxin caused vasodilatation, indicated by a fall in perfusion pressure. 4. Thus a digoxin-like immunoreactive substance, previously reported to be present in the placenta, is released into the fetal circulation and may play a role in placental control of fetal vascular tone.

Systemic and regional haemodynamic interactions between K+ channel openers and the sympathetic nervous system in the pithed SHR

1. The interactions between two K+ channel openers, cromakalim and SR 44866 (infused i.v. at equihypotensive doses), and the sympathetic nervous system at the systemic and regional (mesentery, kidney, hindlimb) vascular levels were investigated in the pithed spontaneously hypertensive rat (SHR) by use of the pulsed Doppler technique. 2. The two K+ channel openers did not affect postsynaptic alpha 1- but slightly reduced postsynaptic alpha 2-adrenoceptor mediated systemic pressor and regional vasoconstrictor responses. 3. Both drugs significantly decreased the systemic pressor and regional vasoconstrictor responses elicited by spinal cord stimulation. These sympathoinhibitory effects were not homogeneously distributed among the different vascular beds, the decreasing rank order being: mesentery greater than kidney greater than hindlimb. Simultaneously, the spinal cord stimulation-induced tachycardia remained unaffected. 4. After treatment with K+ channel openers, restoration of initial blood pressure and vascular tone values by infusion of prostaglandin F2 alpha (PGF2 alpha) and vasopressin respectively did not affect and abolished the sympathoinhibitory effects of cromakalim and SR 44866. 5. We conclude that in SHRs the two K+ channel openers that we investigated exert similar sympathohibitory effects which affect some vascular beds more than others. These effects are not dependent upon the arterial blood pressure level and are most likely prejunctionally located.

Studies on Prostaglandin and Luteolysis in the Pseudopregnant Rabbit

The ability of pulsatile infusion of prostaglandin F2 alpha (PGF2 alpha) or 13, 14-dihydro prostaglandin F2 alpha to induce corpus luteum regression was examined in the pseudopregnant rabbit. Each prostaglandin was infused in 5, 1-hour pulses (1 per 6 hours) during a 25-hour period starting day 9 or 10 of pseudopregnancy. Although both prostaglandins were capable of inhibiting progesterone secretion, pulse administration was no more effective than continuous infusion. To determine if PGF2 alpha was released into the systemic circulation during spontaneous luteolysis, starting day 12 of pseudopregnancy serial blood samples were collected every 90 minutes from the jugular vein. Prostaglandin F levels remained steady (1-2 ng/ml over the collection period with no apparent increase associated with functional luteolysis. Although prostaglandins may be involved in luteolysis in the rabbit, the present results suggest that it is unlikely that PGF2 alpha by itself is responsible for the sustained fall in progesterone secretion at the end of the pseudopregnancy.

Prostaglandin E1 and Nitroglycerin Effects on Canine Epicardial Conductance and Distal Coronary Resistance Vessels

Prostaglandin E1 (PGE1) has been reported to be a coronary vasodilator and has been considered clinically in the treatment of coronary vasospasm, but its mechanism of action is not known. To evaluate the vasomotor effect of PGE1, epicardial coronary and distal resistance vessel responses were compared by PGE1 and nitroglycerin infusion into the left anterior descending (LAD) artery of the closed-chest dog. Coronary angiography and 133Xe washout flow measurements were used to quantitate proximal and distal vessel responses, respectively. To evaluate potential inhibitory actions, vessels were contracted by continuous LAD infusion of prostaglandin F2 alpha (PGF2 alpha) or serotonin before dose-response testing with PGE1 or nitroglycerin. PGE1 alone produced a 20% dilation of the LAD in vivo but only with the highest dose (2.0 micrograms/min). PGE1, however, did not reverse epicardial vessel constriction induced by PGF2 alpha or serotonin. LAD flows (resistance vessel response) were increased comparably by PGE1 alone and with PGF2 alpha added (100 and 93% above control flow, respectively) but to a lesser extent with serotonin added (57% above control). In contrast, nitroglycerin completely reversed epicardial artery constrictions induced by PGF2 alpha and serotonin. Our findings indicate that although PGE1 is a vasodilator in vivo, it does not demonstrate a major effect in dilating epicardial conductance coronary arteries and therefore may not be beneficial in antagonizing endogenous contractile factors in treatment of coronary vasospasm. PGE1 does increase coronary blood flow by dilating distal resistance vessels. The beneficial effects of PGE1 in humans with unstable angina therefore are probably not due to vasorelaxing effects on epicardial coronary conductance arteries.

Colonic α2‐adrenoceptor‐mediated responses in the pony

The motor responses of the caecum and colon to stimulation of alpha 2-adrenoceptors by xylazine and detomidine at the recommended dose levels of 0.6 and 0.1 mg/kg were investigated in three ponies. The motor changes of the left ventral colon induced by continuous intra-arterial infusion of a prostaglandin (PGF2 alpha) were used to assess the relative inhibitory effects of xylazine and detomidine in a colic model. The administration of alpha 2-agonists inhibited the spiking activity on the whole of the large intestine for 20-30 min (xylazine) or 2-3 h (detomidine). However, the detomidine-induced inhibition was preceded by a short period of increased smooth muscle basal tone as indicated by strain-gauge force transducer measurements. This pattern of activity was neither reversed nor prevented by the administration of tolazoline (10 micrograms/kg/min) intra-arterially. In contrast, inhibition of the colonic phasic and tonic motor activity by alpha 2-adrenoceptor stimulation was reversed competitively by tolazoline. The intra-arterial infusion of prostaglandin F2 alpha (10 micrograms/kg/min) induced prolonged and sustained spiking activity that might be related to signs of mild colic. Detomidine, and to a lesser extent xylazine, relaxed the whole of the large intestine and this was accompanied by alleviation of the signs of visceral pain.

Pulmonary blood flow reduction by prostaglandin F2 alpha and pulmonary artery balloon manipulation during one-lung ventilation in dogs.

The purpose of this experimental study was to compare two methods of pulmonary blood flow manipulation during one-lung ventilation (OLV), either reducing pulmonary blood flow to the non-ventilated lung by inflation of a pulmonary artery catheter balloon (PAB) or by infusion of prostaglandin F2 alpha (PGF2 alpha). Seven anaesthetized dogs were intubated with a Kottmeier endobronchial tube and ventilated with 66% O2. Systemic and pulmonary pressures and blood gases, cardiac output and airway pressure were measured, and the venous admixture (QSP/QT) was calculated. During two-lung ventilation (TLV) Pao2 was 43.6 +/- 1.9 kPa (mean +/- s.d.) and (QSP/QT) was 11 +/- 3%. OLV reduced Pao2 to 12.1 +/- 1.6 kPa (P less than or equal to 0.001) and increased QSP/QT to 40 +/- 4% (P less than or equal to 0.001). Mean pulmonary artery pressure and airway pressure increased. PAB inflation caused an increase in Pao2 to 19.9 +/- 2.9 kPa (P less than or equal to 0.02) and a decrease in QSP/QT to 27 +/- 6% (P less than or equal to 0.001). PGF2 alpha infusion (1.2 micrograms kg-1 min-1) into the pulmonary artery of the non-ventilated lung increased Pao2 to 22.4 +/- 3.3 kPa (P less than or equal to 0.001) and decreased QSP/QT to 25 +/- 4 (P less than or equal to 0.001). PGF2 alpha infusion resulted in a small increase in mean systemic and pulmonary artery pressures. During the infusion of 1.2 micrograms kg-1 min-1 of PGF2 alpha no signs of bronchoconstriction were observed. PAB inflation and PGF2 alpha infusion were equally effective in improving oxygenation and reducing venous admixture during OLV.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical sympathectomy decreases alveolar hypoxic vasoconstriction in lambs but not in sheep.

We studied the role of the sympathetic nervous system in the augmented vasoconstrictor response of the newborn lamb, compared with the adult sheep, by producing a chemical sympathectomy with 6-hydroxydopamine (6-OHDA). Seven lambs, age 4-16 days, and five sheep, age 2 yr, were anesthetized and intubated with a double-lumen endotracheal tube, allowing ventilation of one lung with O2 to maintain systemic oxygenation while the contralateral lung was ventilated with N2 as a hypoxic challenge. Distribution of perfusion to each lung was evaluated using positron scintigraphy after inferior vena caval injections of 13N, a positron-emitting isotope. In the lambs, prior to 6-OHDA, distribution of perfusion to the test lung was 43 +/- 3% of total lung perfusion during bilateral O2 ventilation and fell with hypoxia to 24 +/- 2%, a reduction of 44 +/- 3% during N2 ventilation as compared with O2 ventilation. After 6-OHDA, hypoxic challenge reduced perfusion by only 22 +/- 2% (P less than 0.01 compared with pre-6-OHDA). In the adult sheep, hypoxic vasoconstriction reduced perfusion to the test lung by 28 +/- 2% but was unaffected by 6-OHDA. Absence of rise in pulmonary vascular resistance (PVR) or femoral artery pressure (Pfa) in response to Tyramine infusions after 6-OHDA confirmed complete sympathectomy in lambs and sheep. Persistent increases in PVR and Pfa to infusions of prostaglandin F2 alpha before and after 6-OHDA showed that the loss of alveolar hypoxic vasoconstriction in the lamb was specific. Thus sympathetic innervation may contribute to the greater strength of alveolar hypoxic vasoconstriction found in lambs than in sheep.

Low Dose I.V. Infusion of Prostaglandin F2αfor Induction of Labor at Term

In 100 pregnant women at term, labor was induced for medical reasons by i.v. infusion of a low dose of prostaglandin F2 alpha (PGF2 alpha). With a dose not exceeding 6 micrograms PGF2 alpha/min, all patients were induced into labor. The mean induction-delivery time was 6.6 hours and the overall proportion of instrumental deliveries was 19%, including 6% cesarean sections. Very few side effects were observed. It is concluded that i.v. infusion of prostaglandin F2 alpha in a low dose regimen might be considered as an alternative to existing methods for the induction of labor at term.

Effect of severe hypoxia on the pulmonary vascular response to vasoconstrictor agents.

When isolated blood-perfused pig lungs are exposed to inspired O2 tensions (PIO2) below 30 Torr, hypoxic pulmonary vasoconstriction is transient. To determine whether this transience is caused by a decrease in the amount of ATP available for maintenance of smooth muscle contraction, we compared normoxic (PIO2 = 100 Torr) and hypoxic (PIO2 = 10 Torr) dose-response curves to infusions of prostaglandin F2 alpha (PGF2 alpha), angiotensin II (AII), and potassium chloride (KCl). Hypoxia caused reversible depression of the responses to PGF2 alpha and AII but had no effect on the response to KCl. Because during hypoxia the lung was capable of an undiminished vasoconstrictor response to at least one agent, it seems unlikely that the supply of ATP available for contraction was limiting. The mechanism for the transience of the vasoconstrictor response to low PO2 values and the depression of the response to AII and PGF2 alpha remains unknown, but could involve depression of ATP production sufficient to limit some energy-requiring process other than contraction or release of a vasodilator.

Relaxin inhibits spontaneous and prostaglandin-driven myometrial activity in anaesthetized rats.

Porcine relaxin (250 guinea-pig units/mg) infused intravenously into anaesthetized rats at 20 micrograms/h reversibly abolished spontaneous intra-uterine pressure cycles yet left the myometrium responsive to oxytocin in doses of 4--8 mu. The inhibition was found to be primarily of the frequency, rather than of the amplitude, of pressure cycles. Relaxin (5 or 10 micrograms) was capable of completely suppressing uterine activity driven by prostaglandin F2 alpha infusion in oestrogen-treated ovariectomized rats. Whereas the beta-adrenergic blocker, propranolol, had no effect on relaxin-induced inhibition, phentolamine, an alpha-blocker, significantly delayed the relaxin effect. It is unlikely, however, that relaxin operates through an alpha-inhibitory receptor. The results show that relaxin acts primarily as a frequency modulator and is capable of antagonizing an exogenous myometrial stimulant.

Concurrent use of PGF2 alpha, vibrations to the cervix uteri and amniotomy to induce labor after intrauterine fetal death.

A triad consisting of (a) prostaglandin F2 alpha infusion, (b) dilation of the uterine cervix by low frequency vibrations and (c) early low amniotomy was used to induce labor in ten women after intrauterine fetal death had occurred. Vaginal delivery was successful in all cases, with a mean induction-to-delivery interval of 5.4 +/- 0.8 hours. Vibratory dilation effectively prepares the cervix for the intense prostaglandin-induced uterine contractions and thereby reduces the risk of cervical laceration and fistula. The dilation of the cervical canal also makes an early low amniotomy possible and easy. This study demonstrates a highly effective, safe and relatively nontraumatic method for uterine evacuation after intrauterine fetal death.

Long term effects of the anorectic agent fenfluramine alone and in combination with aminorex on pulmonary and systemic circulation in the pig.

We have investigated the effects of chronic oral administration of two anorectic substances, fenfluramine and aminorex, especially on the pulmonary circulation in young pigs with one ligated pulmonary artery. The pulmonary vascular reactivity was tested by alveolar hypoxia, alveolar hyperoxia and infusion of prostaglandin F2ALPHA. No elevation of pulmonary arterial pressures or resistances were found due to the intake of fenfluramine or aminorex over a three month period. The responses to the vasoconstrictor stimuli, hypoxia and prostaglandin F2alpha, and to the vasodilator stimulus, hyperoxia, were equal and not augmented in the drug groups. Fenfluramine or aminorex could therefore could therefore not be shown to have an adverse effect on the pulmonary circulation or on the reactivity of the pulmonary vascular bed in the pig, but fenfluramine elevated systemic arterial pressure.