Smooth muscle pharmacology in the isolated virgin and pregnant rat uterus and cervix.

Uterine smooth muscle function is established, but comparatively little is known about cervical smooth muscle pharmacology. We performed a proof-of-principle experiment that smooth muscle was expressed in the cervix in both virgin and pregnant rats, using the uterus as a comparator. We tested whether all tissues were pharmacologically responsive to contractile and relaxant agonists. Immunohistochemistry revealed the expression of smooth muscle α-actin in all tissues. The isolated tissue bath was used to measure isometric contractility of uterine strips and whole cervices from virgin and pregnant (day 11 ± 2) female Sprague-Dawley rats. We tested classic activators of uterine smooth muscle contraction and relaxation in both uterus and cervix. All tissues contracted to the depolarizing agent potassium chloride, prostaglandin F2α, muscarinic cholinergic agonist carbachol [2-[(aminocarbonxyl)oxy]-N,N,N-trimethylethanaminium chloride], and 5-hydroxytryptamine. Unlike other tissues, the pregnant cervix did not contract to oxytocin, but the oxytocin receptor was present. Both cervix and uterus (virgin and pregnant) had concentration-dependent, near-complete relaxation to the adrenergic agonist norepinephrine and adenylate cyclase activator forskolin [(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-6,10-10b-trihydroxy-3,4a,7,10a-pentamethyl-1-oxo-3-vinyldodecahydro-1H-benzo[f] chroment-5-yl acetate]. The ß-adrenergic receptor agonist isoproterenol was less potent in pregnant cervix versus virgin by ∼10-fold. All tissues, particularly the cervix, responded poorly to the nitric-oxide donor sodium nitroprusside, relaxing ∼20% maximally. These findings support the importance of smooth muscle in the cervix, the use of the isolated cervix in pharmacological studies, and a similarity between smooth muscle pharmacology of the nonpregnant uterus and cervix. This work highlights the unappreciated smooth muscle function of the cervix versus uterus and cervical changes in pharmacology during pregnancy.

Tafluprost protects rat retinal ganglion cells from apoptosis in vitro and in vivo.

BACKGROUND: To investigate whether tafluprost, which is a prostaglandin-related compound and an anti-glaucoma drug, has a direct anti-apoptotic effect in cultured retinal ganglion cells (RGCs) and rat RGCs in retinas with optic nerve crush (ONC). METHODS: RGC-5 cells were induced to undergo apoptosis by a serum deprivation and by exogenous glutamate. The level of cell death with or without tafluprost was monitored by an XTT assay and by immunocytochemistry with activated caspase-3. Changes in intracellular calcium ([Ca(2+)]i) levels were measured with fluo-4 fluorescence. Rat RGCs were degenerated by ONC. After topical instillation of tafluprost for 7 and 14 days, the numbers of retrograde-labeled RGCs were counted. Retinal flatmounts were subjected to terminal dUTP nick end labeling (TUNEL) staining to detect apoptotic cells. RESULTS: Tafluprost dose-dependently promoted RGC-5 cell viability with an optimum concentration of 3 microM (p = 0.006). Tafluprost significantly reduced caspase-3-positive cells and suppressed [Ca(+2)]i evoked by exogenous glutamate. The cGMP-dependent protein kinase inhibitor and KT-5823 partially blocked the rescue effect of tafluprost (p = 0.002). The survival rate of RGCs significantly increased in eyes treated with tafluprost (p = 0.01), and the prevalence of TUNEL-positive cells was significantly decreased 14 days after ONC (p < 0.001). CONCLUSIONS: These data suggest that tafluprost has an anti-apoptotic effect in RGCs.

15-Hydroxy-5,8,11,13-eicosatetraenoic acid inhibits human vascular cyclooxygenase. Potential role in diabetic vascular disease.

Human umbilical arteries converted arachidonic acid to three hydroxyeicosatetraenoic acids (HETEs) as well as prostaglandins. The mono-HETEs have been identified by reverse-phase high pressure liquid chromatography and gas chromatography-mass spectroscopy as 15-HETE and 11-HETE. 15-HETE in arterial segments appears to be derived mainly via the 15-lipoxygenase pathway, whereas 11-HETE, and the presumed di-HETE(s) were products of cyclooxygenase. Nordihydroguaiaretic acid, a lipoxygenase inhibitor, stimulated prostanoid production with a concomitant inhibition of 15-HETE formation. These results suggested that 15-HETE may function as an endogenous regulator of prostacyclin. In human umbilical arterial microsomes, 15-HETE was found to inhibit 6-keto-prostaglandin F1 alpha and total prostanoid production in a concentration-dependent manner (median inhibition constant [IC50] of 52 +/- 3 and 63 +/- 4 microM respectively). The relative distribution of prostaglandins, however, remained unaffected, indicating that the site of action was cyclooxygenase. Kinetic analysis revealed that 15-HETE was a competitive inhibitor of the enzyme. Although no changes in maximum velocity occurred, the apparent Km was significantly different (9.3 +/- 6.9 microM [1 SD] for control vs. 37.6 +/- 17.7 microM for the 15-HETE-treated enzyme). Furthermore, the inhibitory effect of 15-HETE on prostacyclin production was confirmed using cultured bovine endothelial cells. In this cell system, not only did 15-HETE inhibit endogenous prostacyclin production, but also the conversion of exogenous [1-14C]arachidonic acid to prostacyclin (IC50 of 40 +/- 17 microM). No effect on arachidonic acid release was noted. To investigate whether our in vitro finding that 15-HETE inhibited prostacyclin production could be relevant to the in vivo situation, our final studies were performed on vasculature obtained from the diabetic milieu. We found that the production of 15-HETE was significantly increased in vasculature obtained from the infant of the diabetic mother (1.14 +/- 0.26 pmol/mg) when compared to control neonates (0.77 +/- 0.22; P less than 0.01). A concomitant decrease in prostacyclin production was seen (51.6 +/- 12.6 pmol/mg in infants of diabetic mothers vs. 71 +/- 22.3 in controls). Moreover, an inverse correlation between these two eicosanoids was also noted. Our results suggest a potential in vivo regulatory role for 15-HETE on prostacyclin production.

Regulation of mammary and adipose tissue lipoprotein lipase and blood triacylglycerol in rats during late pregnancy. Effect of prostaglandins.

The effects of several prostaglandins on lipoprotein lipase activity of mammary gland and adipose tissue and serum triacylglycerol were studied during late pregnancy in rats. Prostaglandins were injected twice daily for 2 days before and once on the day of analysis. In rats pregnant 20 days, prostaglandin F(2alpha) (PGF(2alpha)) increased the activity of lipoprotein lipase in mammary gland fourfold, reduced the activity in adipose tissue about 60%, and decreased serum concentration of triacylglycerol 50%. PGF(2alpha) also reduced serum concentration of progesterone 90% and increased that of prolactin fivefold, but had no effect on serum concentrations of either immuno-reactive insulin or 17beta-estradiol. Injections of 13,14-dihydro-15-keto PGF(2alpha), a metabolite of PGF(2alpha), had similar effects in rats pregnant 20 days, whereas prostaglandins E(1) and E(2) did not. In rats pregnant 16 days, PGF(2alpha) did not affect lipoprotein lipase activity in the tissues or the concentration of triacylglycerol and prolactin in serum, although it decreased serum progesterone 80%.2-Br-alpha-ergocryptine prevented the increase in serum prolactin in response to PGF(2alpha), but did not alter the effect of PGF(2alpha) on lipoprotein lipase activity or serum triacylglycerol. Progesterone completely blocked the effects of PGF(2alpha) on lipoprotein lipase activity and serum triacylglycerol and prolactin concentrations. These findings indicate that the changes in lipoprotein lipase activity and serum triacylglycerol in PGF(2alpha)-treated rats are probably related to the inhibitory action of PGF(2alpha) on progesterone secretion. They also suggest that endogenous F prostaglandins may play a role in the regulation of lipoprotein lipase activity in mammary gland and adipose tissue near parturition.

Effects of TMB-8, a calcium antagonist, on transport properties of the isolated canine tracheal epithelium.

The effects of the putative intracellular Ca2+ antagonist, TMB-8 (8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate), on the canine tracheal epithelium were examined. Luminal addition reduced rapidly, but reversibly, the transmucosal potential difference and increased the resistance across the open-circuited epithelium. Under short-circuit conditions, the drug reduced stimulation by prostaglandin E2, forskolin, 8-bromo cyclic AMP, prostaglandin F2 alpha and A23187. Inhibition of prostaglandin E2 responses were accompanied by reversal of net Cl- fluxes produced by the agonist. The effects of TMB-8 were unaffected by increasing Ca2+ in the bathing solutions, and were not mimicked by procaine, nitrendipine, calmidazolium, compound 48/80 or trifluoperazine. W7 did, to a limited extent, produce similar responses, though the drug was more toxic, and the effects were irreversible.

Responses of isolated dog arteries to amrinone.

Helically-cut strips of dog cerebral, coronary, mesenteric, renal and femoral arteries contracted with prostaglandin (PG) F2 alpha or K+ responded to amrinone (10(-5) to 10(-4) mol X litre-1) with relaxation, which was not influenced by treatment with propranolol, atropine, cimetidine, aminophylline or aspirin. The contractile response of mesenteric arteries to transmural electrical stimulation (2, 5 and 20 Hz) and noradrenaline was attenuated by amrinone (3 X 10(-5) and 10(-4) mol X litre-1); the attenuation of the response to nerve stimulation and noradrenaline did not significantly differ. Ca2+-induced contractions in mesenteric arteries exposed to Ca2+-free media and depolarised by excess K+ were inhibited by amrinone, and the inhibition could not be reversed by the addition of excess Ca2+. Treatment with amrinone potentiated the relaxant responses of mesenteric arteries to adenosine but did not alter the response to isoprenaline. Amrinone in concentrations sufficient to produce moderate and marked relaxation did not significantly alter the content of cyclic AMP in mesenteric arteries. Attenuation by amrinone of the contractile response to transmural stimulation, noradrenaline and Ca2+ and the relaxation of a variety of arteries induced by amrinone may not be due to interference with the transmembrane influx of Ca2+ and intracellular accumulation of cyclic AMP but to a nonspecific action on arterial smooth muscle. Amrinone appears to increase the metabolic vasodilatation by potentiating the vasodilator action of adenosine.

Increased eicosanoid levels in the Sugen/chronic hypoxia model of severe pulmonary hypertension.

Inflammation and altered immunity are recognized components of severe pulmonary arterial hypertension in human patients and in animal models of PAH. While eicosanoid metabolites of cyclooxygenase and lipoxygenase pathways have been identified in the lungs from pulmonary hypertensive animals their role in the pathogenesis of severe angioobliterative PAH has not been examined. Here we investigated whether a cyclooxygenase-2 (COX-2) inhibitor or diethylcarbamazine (DEC), that is known for its 5-lipoxygenase inhibiting and antioxidant actions, modify the development of PAH in the Sugen 5416/hypoxia (SuHx) rat model. The COX-2 inhibitor SC-58125 had little effect on the right ventricular pressure and did not prevent the development of pulmonary angioobliteration. In contrast, DEC blunted the muscularization of pulmonary arterioles and reduced the number of fully obliterated lung vessels. DEC treatment of SuHx rats, after the lung vascular disease had been established, reduced the degree of PAH, the number of obliterated arterioles and the degree of perivascular inflammation. We conclude that the non-specific anti-inflammatory drug DEC affects developing PAH and is partially effective once angioobliterative PAH has been established.

3-Phenyl-5-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]indole-2-carbonitrile, a potent inhibitor of prostaglandin synthetase and of platelet aggregation.

A number of indoles containing the 2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl side chain have been prepared by standard methods. Alternate, novel syntheses of indole-2-carboxamides and indole-2-carbonitriles have been developed. The title compound, 7e, was found to be a potent inhibitor of bovine prostaglandin synthetase in vitro and to lower serum prostaglandin levels after oral or intraperitoneal administration to rats. Consistent with prostaglandin synthetase inhibition, 7e prevented arachidonic acid induced diarrhea in mice and also collagen, ADP, or epinephrine induced platelet aggregation in human platelet-rich plasma. In contrast to many prostaglandin synthetase and platelet-aggregation inhibitors, 7e had neither ulcerogenicity nor systemic antiinflammatory activity in rats.

Pharmacology on rat ileum of certain 2-substituted 3-(dimethylamino)-5,6-dimethoxyindenes related to 5,6-(methylenedioxy)indene calcium antagonists.

Whereas the 2-propyl- and 2-butyl-5,6-(methylenedioxy)indene calcium antagonists reversed the spasmogenic action of several agonists including PGF2alpha and acetylcholine at 5 X 10(-5) to 10(-4) M on the rat ileum, the corresponding 5,6-dimethoxy analogues exhibited spasmogenic activity at higher concentration (10(-4)-10(-3) M) and exhibited neither spasmogenic nor spasmolytic activity at lower (10(-6)-10(-5) M) concentration. The results are compared to the methyl and 2-ethyl analogues. At 10(-4) M only the butyl analogue was capable of moderate antagonism of acetylcholine and at 10(-3) M all four analogues were capable of moderately antagonizing the actions of acetylcholine.

2-Indanpropionic acids: structural leads for prostaglandin F2alpha antagonist development.

A rationale is presented for the development of prostaglandin F2alpha receptor antagonists. The target analogue, 5,6-(dibenzyloxy)-1-oxo-2-propyl-2-indanpropionic acid (3), was shown to have selective activity for antagonism of PGF2alpha when compared to the antagonism of acetylcholine and KCl on the mouse ileum, whereas other 2-indanpropionic acids (1, 2, 4), not substituted with benzyl functions, were considerably less active and nonselective. The results suggest that 3 may serve as a lead compound for further drug development.

Reflex bradycardia and hypotension produced by prostaglandin F2alpha in the cat.

1 Intravenous administration of prostaglandin F2alpha results in a dose-dependent increase in pulmonary arterial pressure, decrease in systemic arterial pressure and a delayed bradycardia. Pulmonary vasoconstriction was observed at doses as low as 0.1 and 0.3 mug/kg. The systemic depressor and heart rate lowering effects were observed at 1 mug/kg doses and above. 2 A moderate bradycardia was still observed after atropine blockade but was abolished following bilateral vagotomy. Neither of these procedures affected the pulmonary vascular response. 3 Injections of submaximal doses of prostaglandin F2alpha (1--4 mug/kg) produced a greater and longer lasting bradycardia when injected into the left atrium than was observed following intravenous administration. In addition the latency of onset was much shorter following left atrial injection. These doses resulted in no change in heart rate and a minimal hypotension when injected into the brachiocephalic artery or into the aortic arch. 4 Small doses of prostaglandin F2alpha administered at the level of the origin of the coronary arteries produced marked decreases in heart rate and blood pressure whereas no change occurred following injection of the same amount into the ascending aorta at more distal sites. 5 These results suggest that prostaglandin F2alpha produces bradycardia and hypotension in the cat by activating 'receptors' located in the left heart or by acting on structures perfused by means of the coronary arteries.

The effects of prostaglandins E1, E2 and F2alpha on the cutaneous vasculature of the rat.

1 The responses of the rat cutaneous vasculature to prostaglandins E1, E2 and F2alpha have been investigated by a photomicrographic technique. 2 Prostaglandin E1 produced transient arterial constriction which was blocked by local pretreatment of preparations with compound 48/80 or methysergide. It was concluded that prostaglandin E1 produced vasoconstriction by release of 5-hydroxytryptamine (5-HT) from mast cells. The magnitude of the vasoconstrictor response appeared to be subject to seasonal variation. 3 Prostaglandin F2alpha produced arterial constriction of longer duration which was not blocked by compound 48/80, methysergide or phenoxybenzamine. 4 Preparations pretreated with prostaglandin F2alpha were found to be more sensitive to the venous constrictor effect, and less sensitive to the arterial constrictor effect, of noradrenaline. 5 Prostaglandin E2 produced arterial constriction which was usually partially blocked by compound 48/80 and methysergide and it was concluded that a major component of the vasoconstrictor response to prostaglandin E2 was of the E1 type but some component was of the F2alpha type.

Effects of yohimbine, rauwolscine and corynanthine on contractions and calcium fluxes induced by depolarization and prostaglandin F2 alpha in rat aorta.

The effects of the selective alpha 2-adrenoceptor antagonists yohimbine and its stereo-isomer rauwolscine and the selective alpha 1-adrenoceptor antagonist corynanthine (a third yohimbine stereoisomer) on contractions induced in rat aorta by depolarization and prostaglandin F2 alpha (PGF2 alpha) have been compared. In calcium-free solution, depolarization with 100 mM K+ failed to produce a contraction of rat aorta but PGF2 alpha (3 microM) stimulated a contraction equal to about 23% of maximal elicited in normal physiological solution. Yohimbine had no significant effect on depolarization-induced contractions except at concentrations greater than 30 microM. Rauwolscine and corynanthine (1 to 100 microM) depressed depolarization-induced contractions in a concentration-dependent manner, but the characteristics of inhibition were not identical. Contractions induced by PGF2 alpha (3 microM) were depressed in a concentration-dependent manner by rauwolscine (3 to 100 microM) but were unaffected by yohimbine or corynanthine. Depolarization-stimulated 45Ca influx was depressed by rauwolscine and corynanthine to about the same extent as were the contractions; while rauwolscine (100 microM) completely inhibited PGF2 alpha-stimulated 45Ca influx, it also depressed part of the PGF2 alpha-stimulated contraction dependent on intracellular calcium. Rauwolscine (100 microM) partly inhibited PGF2 alpha-stimulated release of 45Ca from aortic smooth muscle in calcium-free solution. It is concluded that the yohimbine structure possesses a calcium entry blocking action as well as a depressant action on contractions not dependent on calcium entry. The predominant effect depends on the structural configuration and the nature of the stimulating agent.

Modulation by endothelium of contractile responses in rat aorta in absence and presence of flunarizine.

The possible modulation by endothelium of phenylephrine- and prostaglandin F2 alpha-induced mobilization of calcium for contraction in the rat aorta has been investigated. Contractions elicited by these and other agonists are inhibited in the presence of endothelium. For any single concentration of phenylephrine in the presence of endothelium, the initial phasic components of contractions were significantly greater, the maximal contractions were achieved sooner and were less well maintained as compared to contractions elicited in the absence of endothelium. The kinetic characteristics of contractions stimulated by single concentrations of PGF2 alpha were similar in the presence and absence of endothelium and did not exhibit initial phasic components of contraction. Sub-maximal contractions-elicited by both PGF2 alpha and phenylephrine in the absence of endothelium were inhibited to a greater extent by flunarizine 3 microM than equieffective contractions elicited in the presence of endothelium. Maximal contractions elicited by phenylephrine (1 microM) were inhibited to a similar extent by flunarizine in the presence and absence of endothelium, but maximal contractions elicited by PGF2 alpha (30 microM) were inhibited by flunarizine to a greater extent in the presence than in the absence of endothelium. It is concluded that an endothelium-derived factor, perhaps distinct from endothelium-derived relaxing factor, can modulate the ability of both phenylephrine and PGF2 alpha to mobilize calcium for contraction. This modulatory effect is associated with an enhanced mobilization of intracellular calcium. Thus, submaximal concentrations of both agonists were less dependent on extracellular calcium than on intracellular calcium to elicit contractions in the presence of endothelium, as compared to contractions elicited in the absence of endothelium.

Modification of myometrial activity in vivo by administration of cyclic nucleotides and theophylline to the pregnant rat.

Myometrial activity was recorded in vivo in unrestrained pregnant rats from day 19 of gestation using radiotelemetry. The effects of short-term infusions of theophylline, dibutyryl cyclic AMP and 8-bromo-cyclic GMP were investigated. All three compounds caused a decrease in oxytocin-induced, prostaglandin F2alpha-induced and spontaneous uterine activity. After cessation of the infusion of these compounds uterine activity returned to near pre-infusion levels within approximately 15 min in most animals. The possible roles of cyclic nucleotides in the control of myometrial contraction are discussed in the light of these observations.

Simultaneous infusion of prostaglandin E2 antagonizes the luteolytic action of prostaglandin F2alpha in vivo.

Corpora lutea of ewes bearing ovarian autotransplants were infused for 4 h with prostaglandin F2alpha (PGF2alpha) (10 microng/h), PGF2alpha+PGE2 (10microng/h of each), PGE2 (10 microng/h) or saline on day 10 of the cycle. Ovarian venous blood obtained before, during, and up to 12 h after the infusion period, was assayed for progesterone. Prostaglandin F2alpha produced an immediate, rapid and sustained decline in progesterone secretion, but infusion of PGE2 together with PGF2alpha prevented the decline until after the infusion. Progesterone secretion was unaffected by infusion of PGE2 alone. Oestrous behaviour was observed in four out of seven animals infused with PGF2alpha but in only one out of six infused with PGF2Alpha+PGE2. None of the animals infused with PGE2 alone or saline only came into heat.

Inhibitory effect of progesterone on the lactogenic and abortive action of prostaglandin F2alpha.

The effect of ovariectomy, progesterone and prolactin treatment on the action of prostaglandin F2alpha (PGF2alpha) was determined in pregnant rats. PGF2alpha (150 mug times 2) injected i.p. on day 1. or 18 of pregnancy induced lactogenesis about 25 h later and abortion on days 20 and 21 of pregnancy. Treatment with PGF2alpha (100 mug times 2 or 50 mug times 2) on day 19 induced lactogenesis around 22 or 38 h later, respectively, and abortion on day 21. PHF2alpha treatment on day 17 was less effective. Unilateral ovariectomy on day 17 of pregnancy induced lactogenesis 32 h later but not abortion. PGF2alpha (150 mug times 2) given on the day of surgery advanced lactogenesis 12 h and rats aborted on day 19. Bilateral overiectomy on day 17 induced abortion between days 20 to 21, but if a single dose of PGF2alpha (300 mug) was injected on day 18. all the ovariectomized rats aborted on day 19. Progesterone (10 mg) injected into rats treated with PGF2alpha (150 mug times 2) on day 18, prevented abortion and delayed lactogenesis. Prolactin (1 mg times 4) treatment delayed only abortion. Serum prolactin levels were significantly higher 12 h after the last dose of PGF2alpha (150 mug times 2) in rats treated on days 17, 18 or 19 of pregnancy. Pretreatment with progesterone prevented the rise in prolactin concentration. These result suggest that the lactogenic and abortive action of PGF2alpha may be dependent on the uterine and plasma concentration of progesterone.

Pre-ovulatory elevation of rat ovarian prostaglandins F, and its blockade by indomethacin.

Prostaglandins of the F series have been measured, by radioimmunoassay, in ovaries of prepubertal rats in which first estrus was synchronized by injection of pregnant mare serum gonadotropin. Marked elevations, up to 20-fold, were observed approximately in parallel with the endogenous luteinizing hormone surge which occurs on the evening of proestrus, and within 4 h after injection of exogenous luteinizing hormone on the morning of proestrus. Injection of indomethacin, 0.8 mg per rat, at 14:45 on proestrus, prevented the increase in ovarian prostaglandins F without significantly reducing the proestrous elevation of serum luteinizing hormone. These observations support elevation of serum luteinizing hormone. These observations support a physiologic role of prostaglandins F in rat ovarian responses to luteinizing hormone.

Pilocarpine antagonizes prostaglandin F2 alpha-induced ocular hypotension in monkeys. Evidence for enhancement of Uveoscleral outflow by prostaglandin F2 alpha.

Twice daily topical application of 50 micrograms of prostaglandin F2 alpha tromethamine to cynomolgus monkey eyes produced significant ocular hypotension lasting at least six hours, with the intraocular pressure (IOP) falling between 35% and 50%, ie, to about 8 to 10 mm Hg, following the seventh dose. A single topical application of 1 mg of pilocarpine hydrochloride produced a much smaller IOP reduction and strong, probably maximal accommodation, both of which lasted at least eight hours. When prostaglandin F2 alpha-treated eyes were given pilocarpine before the seventh dose of prostaglandin F2 alpha, accommodation and IOP responded as in eyes receiving pilocarpine only. Atropine sulfate pretreatment of eyes receiving pilocarpine and prostaglandin F2 alpha completely prevented pilocarpine-induced accommodation and inhibition of ocular hypotension induced by prostaglandin F2 alpha. We hypothesize that (1) prostaglandin F2 alpha reduces IOP by increasing uveoscleral drainage of aqueous humor, and (2) pilocarpine pretreatment contracts the ciliary muscle, obliterating the intramuscular spaces and closing off the uveoscleral drainage pathway and thus physiologically blocking the effect.

Uterine and cardiovascular effects of fenoterol and hexoprenaline in prostaglandin F2 alpha-induced labor in humans.

The effectiveness of the beta-sympathomimetic drugs in prostaglandin-induced labor in humans is uncertain. To assess and compare their uterine and cardiovascular effects, fenoterol (2.5 micrograms/minute) and hexoprenaline (0.38 micrograms/minute) were alternatively infused for 20 minutes in each of 12 patients having prostaglandin F2 alpha inductions of labor at term. Uterine activity was reduced to less than 29% of the pretreatment value. For similar tocolytic effects, hexoprenaline produced a significantly lesser effect on maternal heart rate than fenoterol (P = .005).