Effect of cold pressor stimulation on plasma norepinephrine, dopamine-beta-hydroxylase, and renin activity

Changes in plasma levels of norepinephrine, dopamine-β-hydroxylase (DβH), and renin activity were observed in nine healthy volunteers during cold pressor stimulation. Increases in mean arterial blood pressure and heart rate during cold stimulation were accompanied by a sharp rise in plasma norepinephrine, while plasma DβH and renin activity showed little or no change. The results indicate that plasma norepinephrine accurately reflects acute activation of the sympathetic nervous system in contrast to plasma DβH and renin activity.     

Comparative effects of rauwolscine, prazosin, and phentolamine on blood pressure and cardiac output in anesthetized rats

The endogenous role of the alpha-adrenergic system in the maintenance of mean arterial pressure (MAP), total peripheral resistance (TPR), cardiac output (CO) and its distribution, and plasma norepinephrine and epinephrine release was investigated by the administration of selective alpha-adrenoceptor antagonists to halothane-anesthetized rats. The blockade of alpha 1-, alpha 2-, and both alpha 1- and alpha 2-receptors was accomplished by i.v. infusions of prazosin, rauwolscine, and phentolamine, respectively. The microsphere technique was used for the determination of CO and its distribution. Since the infusions of the three antagonists caused similar decreases of MAP and heart rate, the results suggest that postjunctional alpha 1- and alpha 2-receptors are both important in the control of MAP. During the infusion of prazosin, TPR was decreased but CO was not changed. In contrast, CO was decreased but TPR was not changed during the infusions of rauwolscine and phentolamine. Thus, CO was reduced after the blockade of alpha 2- but not alpha 1-receptors. All three antagonists caused an increase in percent distribution of CO to the lungs and muscle, suggesting that the sympathetic nervous system plays the greatest vasoconstrictor influence in the lungs and muscle via stimulations of both subtypes of alpha-adrenoceptors. The administration of either prazosin or rauwolscine caused little change in plasma catecholamine levels. In contrast, phentolamine caused large increases in both epinephrine and norepinephrine levels. Therefore catecholamine release was only increased after concurrent blockade of both alpha 1- and alpha 2-adrenoceptors.     

Plasma catecholamines and dopamine-beta-hydroxylase activity in spontaneously hypertensive rats.

Levels of plasma norepinephrine and total catecholamines in spontaneously hypertensive rats bred from a normotensive Kyoto strain of Wistar rats increase between their 8th to 12th week post utero concomitant with the development of hypertension, but levels of plasma norepinephrine are not significantly different between the spontaneously hypertensive strain, a normotensive Kyoto strain and a N.I.H. strain of Wistar rats at either 8 or 12 weeks of age. Plasma total catecholamine levels in the spontaneously hypertensive strain are significantly higher at 12 weeks of age than those in either control strain, while plasma levels of dopamine-β-hydroxylase show no consistant relationship between the three strains. It, therefore, appears unlikely that increased sympathetic neuronal activity is an etiological factor in this form of hypertension.     

The influence of aging on the human sympathetic nervous system and brain norepinephrine turnover

Investigating aging effects on the sympathetic nervous system and ascertaining underlying central nervous system (CNS) mechanisms mediating sympathetic stimulation is clinically pertinent because of the possible interconnection of cardiovascular disease development with age-dependent sympathetic nervous changes. Because of previous evidence linking human CNS neuronal noradrenergic function and sympathetic activity, we investigated the influence of aging on brain norepinephrine turnover in 22 healthy men aged 20-30 yr and 16 healthy men aged 60-75 yr by measuring the internal jugular venous overflow of norepinephrine and its lipophilic metabolites. Sympathoneural and adrenal medullary function was also studied, using plasma catecholamine isotope dilution methodology and regional central venous sampling. In the older men there was increased norepinephrine turnover in suprabulbar subcortical brain regions, 317 +/- 50 ng/min compared with 107 +/- 18 ng/min in younger men. A differentiated sympathetic nervous activation was also present in older men. Overall, levels of both cardiac and hepatomesenteric norepinephrine spillover were directly correlated with subcortical norepinephrine turnover. These findings suggest that in sympathetic nervous activation accompanying aging, as has previously been demonstrated with the sympathetic nervous stimulation in human hypertension and heart failure, there is an underlying sympathoexcitatory influence of noradrenergic projections to suprabulbar subcortical regions.     

Effects of exogenous prostaglandin E1 on human plasma norepinephrine level and dopamine-beta-hydrolyxase activity.

Effects of exogenous PG E1 on the level of human plasma norepinephrine (NE), dopamine-beta-hydroxylase (DBH) activity, cAMP, cGMP, free fatty acids (FFA) as well as pulse rate and blood pressure were studied. Significant decreases of blood pressure and increases of pulse rate were observed after 20 min of the infusion of 0.05 microgram/kg/min of PG E1. The level of plasma NE increased by 174% (p less than 0.005) after the infusion. However, the increase of DBH activity was not significant. There was a tendency of increase of plasma level of FFA. These results suggested that the infusion of PG E1 caused an augmented sympathetic nervous activity due to systemic hypotension induced by PG E1.     

Antecedent short-term central nervous system administration of estrogen and progesterone alters counterregulatory responses to hypoglycemia in conscious male rats

The aim of this study was to test the hypothesis that antecedent short-term administration of estradiol or progesterone into the central nervous system (CNS) reduces levels of neuroendocrine counterregulatory hormones during subsequent hypoglycemia. Conscious unrestrained male Sprague-Dawley rats were studied during randomized 2-day experiments. Day 1 consisted of an 8-h lateral ventricle infusion of estradiol (1 mug/mul; n = 9), progesterone (1 mug/mul; n = 9), or saline (0.2 mul/min; n = 10). On day 2, a 2-h hyperinsulinemic (30 pmol.kg(-1).min(-1)) hypoglycemic (2.9 +/- 0.2 mM) clamp was performed on all rats. Central administration of estradiol on day 1 resulted in significantly lower plasma epinephrine levels during hypoglycemia compared with saline, whereas central administration of progesterone resulted in increased levels of plasma norepinephrine and decreased levels of corticosterone both at baseline and during hypoglycemia. Glucagon responses during hypoglycemia were unaffected by prior administration of estradiol or progesterone. Endogenous glucose production following day 1 estradiol was significantly lower during day 2 hypoglycemia, and consequently, the glucose infusion rate to maintain the glycemia was significantly greater after estradiol administration compared with saline. These data suggest that 1) CNS administration of both female reproductive hormones can have rapid effects in modulating levels of counterregulatory hormones during subsequent hypoglycemia in conscious male rats, 2) forebrain administration of reproductive hormones can significantly reduce pituitary adrenal and sympathetic nervous system drive during hypoglycemia, 3) reproductive steroid hormones produce differential effects on sympathetic nervous system activity during hypoglycemia, and 4) reduction of epinephrine resulted in significantly blunted metabolic counterregulatory responses during hypoglycemia.     

Glucocorticoid suppression of the sympathetic nervous system and adrenal medulla

Studies were performed to evaluate the effects of glucocorticoids on the activity of the sympathetic nervous system and adrenal medulla. Plasma concentrations of norepinephrine and epinephrine were measured in rats in which endogenous glucocorticoids were removed by bilateral adrenalectomy and in rats to which exogenous glucocorticoids were administered. In intact rats, dexamethasone (2.5, 25 or 250 micrograms) pretreatment suppressed ether vapor-induced elevations of norepinephrine and epinephrine concentrations in plasma. Corticosterone (3 mg/kg), similar to dexamethasone, attenuated the elevation of plasma concentrations of norepinephrine and epinephrine in rats exposed to ether vapor. Glucocorticoids did not alter the elevation of plasma catecholamines stimulated by intracerebroventricular injections of corticotropin-releasing factor or calcitonin gene-related peptide, thus demonstrating functional integrity of the sympathetic nervous system and adrenal medulla. Adrenalectomy resulted in elevation of basal plasma norepinephrine levels and accentuation of ether vapor-induced elevations of plasma norepinephrine concentrations in rats. Dexamethasone (25 ug) administration blunted the effects of adrenalectomy on both basal and ether vapor-stimulated levels of plasma norepinephrine. It is concluded that glucocorticoids acting at as yet undefined sites may be involved in the regulation of sympathetic nervous system and adrenal medullary function.     

Catecholamines and dopamine-β-hydroxylase activity during therapeutic abortion induced by sulprostone

To evaluate the changes in circulating norepinephrine (NE), epinephrine (E) and dopamine-β-hydroxylase (DBH) caused by an intravenous infusion of a derivate of PGE₂, sulprostone, in connection with legal termination of pregnancy, serial plasma samples were analyzed for six gravidae. Plasma catecholamines were measured by a sensitive radioenzymatic method (9,10) and DBH activities by a photometric assay (11). Intravenous infusion of sulprostone, in abortifacient doses as an intravenous infusion of 3–4 μg per minute for six to eight hours produced a decrease in circulating norepinephrine. No significant alteration was found in plasma epinephrine or dopamine-β-hydroxylase activity. The finding suggests an inhibitory effect of sulprostone on the release of norepinephrine from the adrenergic terminals without inhibition of the adrenal medulla.     

Dissociation of hyperthermic and hyperglycemic effects of central prostaglandin F2 alpha.

We previously reported that intraventricular prostaglandins (PGs) produced hyperthermia and hyperglycemia in anesthetized rats. However, the relationship of them is little known. We examined the relationship between hyperthermia and hyperglycemia induced by intraventricular PGF2 alpha using curarized and adrenal demedullated rats. Iv curare completely prevented the PGF2 alpha-induced hyperthermia, but enhanced the hyperglycemic effect of PGF2 alpha. Adrenal demedullation completely prevented the hyperglycemia, but did not affect the hyperthermic effect of PGF2 alpha. To further assess the site of action concerned with PGF2 alpha-induced thermoregulation and glucoregulation in the central nervous system (CNS), we injected saline or PGF2 alpha into the preoptic area of the anterior hypothalamus (POA) in intact rats. After microinjection of PGF2 alpha into the POA, the rectal temperature rose, but the plasma glucose level did not increase significantly, as compared with saline-treated control rats. These results suggest that PGF2 alpha causes the central nervous system to produce hyperthermia via shivering, stimulated the somatic motor system, and to produce hyperglycemia by stimulating central sympathetic outflow to the adrenal medulla, but these operate independently under different neural regulation, and these sensitive sites are organically dissociated in the CNS.     

Effects of beta-adrenergic agonist infusions on myometrial activity and plasma prostaglandin levels in the nonpregnant sheep

Recent studies have reported that beta-adrenergic agonists stimulate the production of stimulatory prostaglandins (PGs) by intrauterine tissues in vitro. These drugs are used clinically to inhibit uterine contractions; consequently an increase in stimulatory PGs in vivo might have potentially adverse effects. We have, therefore, investigated whether beta-adrenergic agonists increase plasma PG concentrations in vivo. Samples of peripheral (aorta) and uterine venous enriched (vena cava) blood from nonpregnant sheep were collected at 15-min intervals for 1 h before, 3 h during, and 1 h postinfusion of either (a) the beta-adrenergic agonist isoproterenol (Isop) at a dose of 0.16 microgram.kg-1.min-1; (b) Isop at a dose of 0.08 microgram.kg-1.min-1; or (c) saline, 1 mL/h via a jugular vein catheter. The sheep were also equipped with intrauterine recording balloons to record intrauterine pressure and myometrial electromyographic (EMG) electrodes to measure EMG activity. Infusion of Isop at 0.16 microgram.kg-1.min-1 produced a significant initial inhibition of uterine activity, although contractions returned (within 60 min) despite continued administration of Isop. Plasma PGE2 (but not PGF2 alpha or 13,14-dihydro-15-keto-PGF2 alpha (PGFM] concentrations were significantly elevated during the Isop infusion. Administration of Isop at 0.08 microgram.kg-1.min-1 produced no effects on uterine contractile activity but was associated with a significant elevation in plasma PGE2 (but not PGF2 alpha or PGFM) concentrations. No changes in plasma PGE2, PGF2 alpha, or PGFM occurred during saline infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential control of adrenal and sympathetic catecholamine release by alpha 2-adrenoceptor subtypes

In the adrenergic system, release of the neurotransmitter norepinephrine from sympathetic nerves is regulated by presynaptic inhibitory alpha2-adrenoceptors, but it is unknown whether release of epinephrine from the adrenal gland is controlled by a similar short feedback loop. Using gene-targeted mice we demonstrate that two distinct subtypes of alpha2-adrenoceptors control release of catecholamines from sympathetic nerves (alpha 2A) and from the adrenal medulla (alpha 2C). In isolated mouse chromaffin cells, alpha2-receptor activation inhibited the electrically stimulated increase in cell capacitance (a correlate of exocytosis), voltage-activated Ca2+ current, as well as secretion of epinephrine and norepinephrine. The inhibitory effects of alpha2-agonists on cell capacitance, voltage-activated Ca2+ currents, and on catecholamine secretion were completely abolished in chromaffin cells isolated from alpha 2C-receptor-deficient mice. In vivo, deletion of sympathetic or adrenal feedback control led to increased plasma and urine norepinephrine (alpha 2A-knockout) and epinephrine levels (alpha 2C-knockout), respectively. Loss of feedback inhibition was compensated by increased tyrosine hydroxylase activity, as detected by elevated tissue dihydroxyphenylalanine levels. Thus, receptor subtype diversity in the adrenergic system has emerged to selectively control sympathetic and adrenal catecholamine secretion via distinct alpha2-adrenoceptor subtypes. Short-loop feedback inhibition of epinephrine release from the adrenal gland may represent a novel therapeutic target for diseases that arise from enhanced adrenergic stimulation.     

Diabetes-induced biochemical changes in central and peripheral catecholaminergic systems

A great variety of alterations have been described in the nervous system of diabetic animals. They are named as diabetic neuropathy and affect the brain, spinal cord and peripheral nerves. In diabetic animals, plasma and tissue catecholamine levels have been reported to be increased, decreased or unchanged, and these disparities have been explained by differences in the tissues selected, severity or duration of diabetes. Dopamine, norepinephrine and epinephrine from different tissues were extracted by absorption onto alumina, and measured by high performance liquid chromatography with electrochemical detection. We found that diabetes alters catecholaminergic systems in a highly specific manner. The dopamine content is reduced in the dopaminergic nigrostriatal system only. Norepinephrine is differently altered in several areas of the sympathetic nervous system. It is increased in cardiac ventricles, and decreased in stellate ganglia and the blood serum. However, it is not altered in the central nervous system. Finally, epinephrine is only altered in the adrenal gland where it is increased, and in the serum where it is reduced. Our results suggest that diabetes reduces the activity of the nigrostriatal dopaminergic system. Changes found at the sympathoadrenal level could be explained by reduced norepinephrine and epinephrine synthesis, with increased storage due to a reduced release from synaptic vesicles.     

The effect of acetylsalicylic acid and indomethacin on the catecholamine- and oxytocin-induced contractility and prostaglandin (6-keto-PGF1 alpha, PGF2 alpha)-production of human pregnant myometrial strips

The effects of acetylsalicylic acid (ASA) and indomethacin (IND) on the epinephrine and oxytocin stimulated contractility and prostaglandin (6-keto-PGF1 alpha, PGF2 alpha) production of superfused myometrial strips from the pregnant human uterus at term are reported. Without preincubation in ASA or IND epinephrine dose-dependently (10 ng/ml to 1 microgram/ml) stimulated the contractility and significantly increased the PG-release of the myometrial strips. The epinephrine induced increase in contractility was correlated to a higher increase in PGF2a production and a decreased 6-keto-PGF1 alpha/PGF2 alpha ratio (5.4 to 1.8). Superfusion of oxytocin increased myometrial contractions and PGF2 alpha release according to dose (3-12 microU/ml). However, 6-keto-PGF1 alpha production was not affected by oxytocin. Myometrial strips preincubated with ASA (100 micrograms/ml) or IND (10 micrograms/ml) demonstrated little spontaneous activity and the PG production was below the detection limit of the RIA. The stimulating effect of epinephrine and oxytocin on the contractility and PGF2 alpha release of the myometrial strips was inhibited significantly. During continuous superfusion of the ASA and IND preincubated myometrial strips with Tyrode's solution the inhibitory effect on spontaneous, epinephrine-, and oxytocin-stimulated contractility and PGF2 alpha release gradually declined over a period of 2 hours. This decrease of the inhibitory effect was more significant in ASA preincubated specimens. Our results demonstrate that spontaneous, epinephrine-, and oxytocin-stimulated contractility and PG release of human myometrial strips can be inhibited by ASA and IND and that this inhibitory effect is reversible. Furthermore our results suggest that in pregnant human myometrium the inhibition of PGF2 alpha production by ASA and IND is more pronounced than that of 6-keto-PGF1 alpha (PGI2).     

Solubilization of histamine H-1, GABA and benzodiazepine receptors.

Dopamine 3-0-sulfate is present in considerable amounts in mammalian plasma and peripheral tissues. Incubation of dopamine 3-0-sulfate (0.1 μmole) with purified bovine dopamine-β-hydroxylase resulted in the formation of free norepinephrine (7.3 × 10^?3 μmole). The conversion to norepinephrine was inhibited by 0.6 mM of fusaric acid, an inhibitor of dopamine-β-hydroxylase. The reaction of dopamine 3-0-sulfate with dopamine-β-hydroxylase followed Michaelis-Menten kinetics. The calculated K_m was 17 mM, different from the K_m for free dopamine (0.1 mM). The incubation medium does not contain any sulfatase activity.     

Evidence for involvement of prostaglandins in central alpha adrenergic activity and LH release in sheep

Circhoral pulsatile release of immunoreactive luteinising hormone (LH) and prostaglandin F2 alpha (PGF2 alpha) occur synchronously into the jugular vein in ovariectomised sheep. Following a 4-hour control period, intra-carotid injections of phentolamine or intramuscular injections of phenoxybenzamine were given to ovariectomised sheep and the pulsatile release of LH and PGF2 alpha was monitored for a further 6 to 8 hours. Phenoxybenzamine caused a fall in LH and PGF2 alpha in jugular venous plasma. Phentolamine also reduced LH significantly but in this case a marked rise in PGF2 alpha as measured by radioimmunoassay (RIA) occurred after very high doses of phentolamine. Interpretation of the latter results was complicated by the fact that phentolamine at high dose levels interfered with the RIA of PGF2 alpha in plasma. Experiments were repeated in ovariectomised sheep with cannulae placed in the lateral ventricles of the brain for sampling cerebrospinal fluid (CSF). In contrast to the previously observed rise in jugular venous PGF2 alpha following high doses of phentolamine, a fall in CSF levels of immunoreactive PGF2 alpha occurred following intracarotid phentolamine or phenoxybenzamine in 3 out of 7 experiments, while no change was observed in the remaining 4 animals. Phentolamine did not reduce LH significantly in animals with intraventricular cannulae. The work provides support for the view that circhoral pulses of immunoreactive PGF2 alpha in sheep are neural in origin and may be related to sympathetic neurotransmission.     

EVIDENCE FOR EXTRANORADRENERGIC DOPAMINE-β-HYDROXYLASE ACTIVITY IN RAT SALIVARY GLAND

—Three days after superior cervical ganglionectomy of adult Sprague-Dawley rats, the levels of endogenous norepinephrine, the uptake process for [³H]norepinephrine and the activity of tyrosine hydroxylase decreased 99 per cent in the ipsilateral salivary gland. In contrast, the activity of dopamine-β-hydroxylase and DOPA decarboxylase fell to 30 per cent of the activity of the contralateral innervated gland. Examination of the cofactor requirements, the characteristics of activation by cupric ion and the immunologic identity of this residual hydroxylase activity indicated that it was authentic dopamine-β-hydroxylase. The residual dopamine-β-hydroxylase in the denervated gland had the same subcellular distribution as the enzyme in the innervated salivary gland. Procedures that caused atrophy or hypertrophy of the acinar cells did not affect the total content of dopamine-β-hydroxylase in the denervated salivary gland. Chemical sympathectomy with 6-hydroxy-dopamine caused a 40 per cent decrement in the serum levels of dopamine-β-hydroxylase but a 30 per cent increase in its activity in the denervated salivary gland. Although denervation caused a complete loss of endogenous norepinephrine in the salivary gland, it resulted in only a 15 per cent decrement in the levels of endogenous octopamine and β-phenylethanolamine, two other products of dopamine-β-hydroxylase.     

Effect of tyramine and guanethidine on dopamine-β-hydroxylase activity and norepinephrine concentrations in vesicular fraction of the heart and plasma of rats

Repeated administration of high doses of tyramine to rats results in a striking increase in plasma levels of norepinephrine (NE) and a marked depletion in tissue content of NE. The drug also may produces a moderate increase in plasma levels of dopamine-β-hydroxylase (DBH) and a decrease in DBH in synaptic vesicles of sympathetic nerves in the heart. The latter effects are prevented by a ganglionic blocking agent, indicating that they may be mediated by neuronal activation secondary to the stress attending the drug administration. Chronic administration of guanethidine, which is reported to destroy most sympathetic nerves produces more marked decrease in plasma NE levels and plasma DBH activity. The possible sources of this activity are discussed.     

Angiotensin II mediates systemic rebound hypertension after cessation of prostacyclin infusion in sheep

Prostacyclin(or epoprostenol), an arachidonic acid metabolite, is aneffective treatment for patients with primary pulmonary hypertension.Interruption of chronic prostacyclin infusion can result in recurrentsymptoms of dyspnea and fatigue. The etiology of this phenomenon isunknown. We hypothesized that sympathoadrenal activation could lead toincreased vascular tone after abrupt termination of the infusion. Toevaluate this effect, we monitored six chronically instrumented, awakesheep during and after infusion of prostacyclin. Prostacyclin decreasedmean arterial pressure (MAP) by 14% and increased cardiac output by33%. After the infusion ceased, MAP rebounded 23% above baseline, andcardiac output decreased by 28% from peak values within 10 min. Wewere unable to demonstrate an increase in norepinephrine levels aftercessation of prostacyclin, nor did -adrenergic blockade affectpostinfusion hemodynamics. However, plasma renin activity increased>10-fold at peak infusion and remained elevated for up to 2 h afterdiscontinuation of prostacyclin. Coinfusion of the angiotensinII-receptor antagonist L-158,809 resulted in complete abrogation of thepostcessation rise in MAP. We conclude that renin-angiotensin systemactivation is primarily responsible for systemic hypertension occurringafter abrupt cessation of prostacyclin infusion in sheep and thatangiotensin II receptor blockade prevents this response. Our data donot support a role for sympathetic nervous system activation in thesystemic pressor response after prostacyclin infusion.

     

Effect of prostaglandin F2 alpha (PGF2 alpha) on sources of progesterone and pregnancy in intact, ovariectomized and hysterectomized 90-100 day pregnant ewes.

A single dose of 8 or 16 mg of PGF2 alpha per 58 kg body weight was injected intramuscular into intact, ovariectomized or hysterectomized 90-100 day pregnant sheep in three separate experiments. Both doses of PGF2 alpha decreased the weights of the corpora lutea (P less than or equal to 0.05) and the concentration of progesterone in ovarian venous plasma at 72 hr (P less than or equal to 0.05) compared to the 0 hr sample within treatment groups and to control ewes at 72 hr in intact and hysterectomized pregnant ewes. In hysterectomized pregnant ewes, progesterone in jugular plasma declined (P less than or equal to 0.05) from 0 to 72 hr but never fell below 4 mg/ml and this decrease in progesterone after 8 or 16 mg PGF2 alpha was greater than in control hysterectomized ewes (P less than or equal to 0.05). There was a significant decrease in progesterone over time in jugular or uterine venous plasma in the presence of absence of the ovaries in 90-100 day pregnant ewes (P less than or equal to 0.05) but the profiles of progesterone were not different between vehicle and PGF2 alpha-treated ewes (P greater than or equal to 0.05). Uterine venous progesterone never declined below 30 ng/ml in the presence or absence of the ovaries and there was a significant quadratic increase (P less than or equal to 0.05) in uterine venous progesterone toward the end of the 72 hr sampling period indicating an increase in steroidogenic activity of the placenta. PGF2 alpha did not affect the number of abortions in intact or ovariectomized pregnant ewes (P greater than 0.05). Thus, the corpus luteum of sheep at 90-100 days of pregnancy is functional and responsive to PGF2 alpha, placentomes are functional but do not appear to be responsive to the doses of PGF2 alpha tested and PGF2 alpha was not an abortifacient over the 72 hr treatment period.     

The effect of indomethacin on ovarian prostaglandin release in hens

Indomethacin, an inhibitor of prostaglandin (PG) synthetase, will block uterine muscle electromyographic activity (EMG activity) and oviposition at a midsequence oviposition and ovulation in domestic hens, but does not block the increase in EMG activity associated with the first ovulation of a sequence. To assess the potential relationship between prostaglandin release from the ovarian follicles and EMG activity in egg-laying hens, we determined the concentrations of PGF2 alpha, 13,14-dihydro-15-keto-PGF2 alpha (PGFM), and PGE2 in brachial, ovarian follicular and uterine venous plasma and tissues in relation to uterine muscle EMG activity at the first ovulation and at a midsequence oviposition. The concentrations were measured after an i.m. injection (25 mg/hen) of indomethacin. In control hens sampled hourly, beginning 4 h before the peak of EMG activity at the first ovulation of a sequence, there was a sharp increase (p less than 0.05) in concentrations of PGF2 alpha and PGFM in brachial vein plasma coincident with the increase (p less than 0.05) in uterine EMG activity. Hens pretreated with indomethacin also had increased plasma PGF2 alpha and PGFM levels (p less than 0.05) in brachial vein plasma and increased uterine EMG activity (p less than 0.05) at this time. Indomethacin treatment lowered but did not eliminate mean levels of PGF2 alpha in the venous effluent from the largest preovulatory follicle at the first ovulation (36.0 +/- 9.9 ng/ml vs. 14.4 +/- 1.8 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)