Cytochemical research on cysts of the sarcosporidian Sarcocystis bovicanis. II. Oxidation-reduction enzymes

By the means of light-microscopic cytological enzymatic methods, the presence of several enzymes (NAD.H and NADP.H-tetrazolium reductases, in addition to alcohol, succinate, isocitrate, glucose-6-phosphate, beta-hydroxybutyrate and glutamate dehydrogenases) has been studied in the tissue cysts of S. bovicanis. A mixed character of oxidative metabolism in the cyst stages is suggested, the involvement of gluconeogenesis being proposed. Neither beta-hydroxybutyrate nor alcohol dehydrogenase activity was demonstrated indicating the absence or a very low rate of lipid metabolism, and suggesting that the process of glycolysis may end with malate formation. From the low activity level of succinate dehydrogenases it is concluded that the citric acid cycle plays presumably a secondary role, if at all, in the energy supply of the cyst stages. Also, a low activity of glucose-6-phosphate dehydrogenases is pointed out. Thus, it is proposed that glycolysis may be primary, if not the only, oxidative pathway in the cyst stages.     

Increased glycolysis in skeletal muscle coordinates with adipose tissue in systemic metabolic homeostasis

Insulin-independent glucose metabolism, including anaerobic glycolysis that is promoted in resistance training, plays critical roles in glucose disposal and systemic metabolic regulation. However, the underlying mechanisms are not completely understood. In this study, through genetically manipulating the glycolytic process by overexpressing human glucose transporter 1 (GLUT1), hexokinase 2 (HK2) and 6-phosphofructo-2-kinase-fructose-2,6-biphosphatase 3 (PFKFB3) in mouse skeletal muscle, we examined the impact of enhanced glycolysis in metabolic homeostasis. Enhanced glycolysis in skeletal muscle promoted accelerated glucose disposal, a lean phenotype and a high metabolic rate in mice despite attenuated lipid metabolism in muscle, even under High-Fat diet (HFD). Further study revealed that the glucose metabolite sensor carbohydrate-response element-binding protein (ChREBP) was activated in the highly glycolytic muscle and stimulated the elevation of plasma fibroblast growth factor 21 (FGF21), possibly mediating enhanced lipid oxidation in adipose tissue and contributing to a systemic effect. PFKFB3 was critically involved in promoting the glucose-sensing mechanism in myocytes. Thus, a high level of glycolysis in skeletal muscle may be intrinsically coupled to distal lipid metabolism through intracellular glucose sensing. This study provides novel insights for the benefit of resistance training and for manipulating insulin-independent glucose metabolism.     

The enzyme activity of carbohydrate metabolism in the liver of swine during the transition from prenatal to postnatal development

Studies have ben been made on the activity of hexokinase, glucokinase, phosphofructokinase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, as well as NADP-dependent dehydrogenases (malate and citrate) in the liver of foetuses and newborn piglets in relation to their age, fasting and reaction to injection of adaptive hormones (insulin and cortisol). It was shown that postpartum adaptation of carbohydrate metabolism in porcine liver is associated with activation of the glycolysis and with the increase in the activity of NADPH-generating dehydrogenases. In fasting newborn piglets the rate of carbohydrate catabolism increases. The effects of the investigated factors are different in the liver of 1-day piglets (sensitive to fasting) and 5-day animals (less sensitive). In is suggested that low ability of newborn piglets to maintain physiological level of glucose in the blood is associated with active glycolysis in the liver and ineffectiveness of the hormone-substrate mechanisms which control tissue glycaemia.     

Garlic supplementation increases peripheral blood flow: a role for interleukin-6?

There is considerable epidemiological and clinical evidence that regular garlic supplementation reduces cardiovascular risk. In this study, we have investigated the hypothesis that dietary garlic supplementation increases tissue blood flow and this is mediated by the vasodilatory actions of interleukin-6 (IL-6). Venous occlusion plethysmography was used to measure resting calf blood flow before and after oral administration of 600 mg of garlic tablets once daily for 7 days in 13 young healthy female volunteers (treatment group) and 13 female controls matched for age and body mass index (BMI). Blood samples were obtained at the time of plethysmography to measure plasma levels of IL-6, nitrate, nitrite and c-GMP. In the treatment group, calf blood flow increased significantly from 3.01 (2.56 to 3.3) ml min(-1) 100 mL(-1) of tissue before garlic to 3.46 (3.0 to 4.03) ml min(-1) 100 mL(-1) of tissue after 7 days of garlic (P = 0.001). Plasma IL-6 concentrations increased significantly from 54.6 (32.3 to 151.6) mcg/mL before to 151 (135.75 to 422.3) mcg/mL after 7 days of garlic (P = 0.02). However, there was no significant change in the plasma levels of nitrate, nitrite and c-GMP after the garlic (P = 0.4, 0.9 and 0.65 respectively). In the control group, resting calf blood flow and plasma levels of IL-6, nitrite, nitrate and c-GMP remained unchanged after 7 days (P = 0.62, 0.92, 0.28 and 0.35 respectively). Calf blood flow showed a non-linear correlation with plasma IL-6 levels after garlic supplementation (r = 0.86, p = <0.001) but not before. There was no significant relationship between blood flow and plasma nitrate, nitrite and c-GMP in either groups and between blood flow and IL-6 in the control group. These data suggest that garlic supplementation increases resting tissue blood flow and this may be mediated by IL-6.     

Effect of acetoacetate on glucose metabolism in the soleus and extensor digitorum longus muscles of the rat.

1. The effect of acetoacetate on glucose metabolism was compared in the soleus, a slow-twitch red muscle, and the extensor digitorum longus, a muscle composed of 50% fast-twitch red and 50% white fibres. 2. When incubated for 2h in a medium containing 5 mM-glucose and 0.1 unit of insulin/ml, rates of glucose uptake, lactate release and glucose oxidation in the soleus were 19.6, 18.6 and 1.47 micronmol/h per g respectively. Acetoacetate (1.7 mM) diminished all three rates by 25-50%; however, it increased glucose conversion into glycogen. In addition, it caused increases in tissue glucose, glucose 6-phosphate and fructose 6-phosphate, suggesting inhibition of phosphofructokinase. The concentrations of citrate, an inhibitor of phosphofructokinase, and of malate were also increased. 3. Rates of glucose uptake and lactate release in the extensor digitorum longus were 50-80% of those in the soleus. Acetoacetate caused moderate increases in tissue glucose 6-phosphate and possibly citrate, but it did not decrease glucose uptake or lactate release. 4. The rate of glycolysis in the soleus was approximately five times that previously observed in the perfused rat hindquarter, a muscle preparation in which acetoacetate inhibits glucose oxidation, but does not alter glucose uptake or glycolysis. A similar rate of glycolysis was observed when the soleus was incubated with a glucose-free medium. Under these conditions, tissue malate and the lactate/pyruvate ratio in the medium were decreased, and acetoacetate did not decrease lactate release or increase tissue citrate or glucose 6-phosphate. An intermediate rate of glycolysis, which was not decreased by acetoacetate, was observed when the soleus was incubated with glucose, but not insulin. 5. The data suggest that acetoacetate glucose inhibits uptake and glycolysis in red muscle under conditions that resemble mild to moderate exercise. They also suggest that the accumulation of citrate in these circumstances is linked to the rate of glycolysis, possibly through the generation of cytosolic NADH and malate formation.     

Carbohydrate metabolism of schistosoma mansoni

1. Schistosoma mansoni utilizes in 1 hour an amount of glucose equivalent to one-sixth to one-fifth of its dry weight. Over 80 per cent of the metabolized glucose is converted to lactic acid by this organism. 2. The rates of glucose utilization and of lactic acid production by S. mansoni are the same under aerobic and under anaerobic conditions. 3. A high rate of lactic acid production and the absence of a postanaerobic increase in the oxygen uptake differentiate S. mansoni from most other parasitic helminths whose metabolism has been studied. 4. Arsenite and p-chloromercuric benzoate inhibit in low concentrations the oxygen uptake and the rate of glycolysis of S. mansoni. This inhibition is not prevented or reversed by an excess of glutathione or of thioglycollate. 5. Fluoride inhibits the removal of glucose and the production of lactic acid by S. mansoni to the same degree. 6. Low concentrations of quinacrine (atabrine) do not affect the respiration or the carbohydrate metabolism of the schistosomes. 7. The inhibitory effect of aldehydes on the metabolism of S. mansoni has been measured. Among this group of compounds dl-glyceraldehyde and o-nitrobenzaldehyde are the most effective inhibitors of glycolysis. 8. In a concentration of 2.6 x 10(-6)M (1:1,000,000) a cyanine dye inhibits almost completely the respiration of the schistosomes, but has no effect on their rate of glycolysis. The oxygen uptake of the worms is inhibited by fuadin to a greater degree than their rate of glycolysis. 2-methyl-1,4-napthoquinone is a much more effective inhibitor of glycolysis than of the respiration of S. mansoni. The latter compound interacts with plasma albumin and, therefore, its inhibitory action on the metabolism of the schistosomes is greatly reduced in human serum or plasma. 9. Evidence is discussed which indicates that, in contrast to glycolysis, respiratory metabolism is not essential for the survival of S. mansoni.     

Effect of cAMP of glycolysis and glycogenolysis in the liver and adrenals of white rats

The rates of glycolysis and glycogenolysis an the rate of lactate formation from glucoso-6-phosphate (G-6-Ph) in the liver were reduced during stress (starvation). On the contrary, these activities in the adrenals were increased. The rates of lactate formation from fructose diphosphate remained unchanged in both organs. The results obtained attest to the inhibition in the liver and activation in the adrenals of phosphorylase, hexokinase and phosphofructokinase. The degree of hexokinase inhibition in the liver depended on the presence of cAMP, ATP and MgCl2 in the incubation medium and was a consequence of enzymatic phosphorylation. Unlike 2', 3'-AMP, the inhibitory effect of CAMP was highly specific. The protein inhibitor of protein kinase completely reversed the inhibitory effect of cAMP on hexokinase. In the adrenals, cAMP slightly increased the rates of glycolysis and lactate formation from G-6-Ph because of allosteric effects of cAMP. The activation rather than inhibition of glycolysis in the adrenals during stress is probably caused by the absence in this tissue of cAMP-dependent protein kinase which phosphorylates hexokinase.     

Muscle energetics during prolonged cycling after exercise hypervolemia

This study examined the question of whether increases in plasma volume (hypervolemia) induced through exercise affect muscle substrate utilization and muscle bioenergetics during prolonged heavy effort. Six untrained males (19-24 yr) were studied before and after 3 consecutive days of cycling (2 h/day at 65% of peak O2 consumption) performed in a cool environment (22-23 degrees C, 25-35% relative humidity). This protocol resulted in a 21.2% increase in plasma volume (P less than 0.05). During exercise no difference was found in the blood concentrations of glucose, lactate, and plasma free fatty acids at either 30, 60, 90, or 120 min of exercise before and after the hypervolemia. In contrast, blood alanine was higher (P less than 0.05) during both rest and exercise with hypervolemia. Measurement of muscle samples extracted by biopsy from the vastus lateralis muscle at rest and at 60 and 120 min of exercise indicated no effect of training on high-energy phosphate metabolism (ATP, ADP, creatine phosphate, creatine) or on selected glycolytic intermediate concentrations (glucose 1-phosphate, glucose 6-phosphate, fructose 6-phosphate, lactate). In contrast, training resulted in higher (P less than 0.05) muscle glucose and muscle glycogen concentrations. These changes were accompanied by blunting of the exercise-induced increase (P less than 0.05) in both blood epinephrine and norepinephrine concentrations. Plasma glucagon and serum insulin were not affected by the training. The results indicate that exercise-induced hypervolemia did not alter muscle energy homeostasis. The reduction in muscle glycogen utilization appears to be an early adaptive response to training mediated either by an increase in blood glucose utilization or a decrease in anaerobic glycolysis.     

Effects of acute administration of doxazosin on fasting and postprandial haemodynamics and lipid metabolism in healthy subjects.

The selective alpha1 -adrenoceptor antagonist doxazosin has apparently beneficial effects on insulin sensitivity and on plasma lipid concentrations. In order to understand these effects better, we investigated the acute effects of doxazosin on adipose tissue and forearm blood flow and on postprandial lipid metabolism in healthy subjects. Nine subjects were studied in a balanced, placebo-controlled design. Pulse rate, blood pressure, forearm and subcutaneous adipose tissue blood flow were measured before and for 6 h after a mixed meal, with concomitant measurements of blood metabolites and insulin. Doxazosin increased pulse rate (p = 0.02) and forearm blood flow (p < 0.01 in fasting state), and decreased vascular resistance in forearm (p < 0.05 for fasting values) and subcutaneous abdominal adipose tissue (p = 0.04). Fasting plasma non-esterified fatty acid concentrations were increased by 40 % (p < 0.05). No other metabolic effects were detected. The effects on adipose tissue vascular resistance and lipolysis (reflected in elevated non-esterified fatty acid concentrations) were unexpected, as these are usually considered to be mediated by the balance of alpha2 - and beta-adrenoceptor activity in humans. We conclude that alpha1 -adrenoceptor activity may be more important in regulation of human lipid metabolism than previously recognized.     

Fructose 2,6-bisphosphate in rat skeletal muscle during contraction.

Fructose 2,6-bisphosphate and several glycolytic intermediates were measured in two rat muscles, extensor digitorum longus and gastrocnemius, which were electrically stimulated in situ. Both the duration and the frequency of stimulation were varied to obtain different rates of glycolysis. There was no relationship between fructose 2,6-bisphosphate content and the increase in tissue lactate in contracting muscle. However, in gastrocnemius stimulated at low frequencies (less than or equal to 5 Hz), there was a 2-fold increase in fructose 2,6-bisphosphate at 10s, followed by a return to basal values, whereas lactate increased only after 1 min of contraction. The concentrations of hexose 6-phosphates, fructose 1,6-bisphosphate and triose phosphates were all increased during the 3 min stimulation. During tetanus (frequencies greater than or equal to 10 Hz) fructose 2,6-bisphosphate was not increased, whereas glycolysis was maximally stimulated and resulted in an accumulation of tissue lactate, mostly from glycogen. The concentrations of hexose 6-phosphate increased continuously during the 1 min tetanus, whereas fructose 1,6-bisphosphate was increased at 10s and then decreased progressively. It therefore appears that fructose 2,6-bisphosphate does not play a role in the stimulation of glycolysis during tetanus; it may, however, be involved in the control of glycolysis when the muscles are stimulated at low frequencies for short periods of time.     

Ex vivo analysis of lactate and glucose metabolism in the rat brain under different states of depressed activity

Brain metabolism of glucose and lactate was analyzed by ex vivo NMR spectroscopy in rats presenting different cerebral activities induced after the administration of pentobarbital, alpha-chloralose, or morphine. The animals were infused with a solution of either [1-(13)C]glucose plus lactate or glucose plus [3-(13)C]lactate for 20 min. Brain metabolite contents and enrichments were determined from analyses of brain tissue perchloric acid extracts according to their post-mortem evolution kinetics. When amino acid enrichments were compared, both the brain metabolic activity and the contribution of blood glucose relative to that of blood lactate to brain metabolism were linked with cerebral activity. The data also indicated the production in the brain of lactate from glycolysis in a compartment other than the neurons, presumably the astrocytes, and its subsequent oxidative metabolism in neurons. Therefore, a brain electrical activity-dependent increase in the relative contribution of blood glucose to brain metabolism occurred via the increase in the metabolism of lactate generated from brain glycolysis at the expense of that of blood lactate. This result strengthens the hypothesis that brain lactate is involved in the coupling between neuronal activation and metabolism.     

Effects of the fetal-placental unit on uterine prostaglandin levels at term in the pregnant rat

Uterine prostaglandins (PGs) increase markedly at term in the pregnant rat. To assess the contribution of the fetal-placental unit (FPU) on uterine tissue and uterine venous blood PG concentrations, each uterine horn of 14 unilaterally pregnant rats at day 21 of pregnancy were compared. In addition, 7 bilaterally pregnant rats were studied. Uterine tissue and uterine venous plasma PGF, PGE, 6-Keto-PGF1 (6KF) and thromboxane B2 (TxB2) and systemic plasma progesterone, estradiol and estrone were determined by radioimmunoassay. Uterine concentrations of PGs (ng/mg DNA) were always greater on the pregnant side of unilaterally pregnant rats (p less than .05) although the PGF levels were elevated to a lesser extent than were PGE, TxB2 or 6KF. However, no differences were detected between uterine tissue from the pregnant side of unilaterally pregnant compared to bilaterally pregnant rats. In addition, no differences were found in uterine venous plasma PGs adjacent or opposite the pregnant uterine horn and in systemic plasma progesterone, estradiol and estrone levels in unilaterally vs bilaterally pregnant rats. These data suggest that the presence of the FPU is associated with an increased capacity of uterine tissue to produce PGE, TxB2 and 6KF, and to a lesser degree PGF, and thus may contribute to the increase in uterine PGs periparturition.     

Human red cell glycolysis in high altitude chronic hypoxia

We have found that glycolysis in human red blood cells under the hypoxic conditions found at high altitudes is connected with changes in enzyme activities and levels of various metabolic intermediates. The sensitivity of the four kinases to hypoxia results in 1) glycolytic hyperactivity leading to a higher intracellular energy state, and 2) accumulation of 2–3 DPG, whose role in the adaptation of red blood cell respiration to high altitude has been shown by previous research. PEP, 3PG, and G6P appear to be the main regulating intermediates in glycolysis in this system. The reason for the very large increase in G1-6DP is still not clear.     

Lactate induces insulin resistance in skeletal muscle by suppressing glycolysis and impairing insulin signaling

Elevation of plasma lactate levels induces peripheral insulin resistance, but the underlying mechanisms are unclear. We examined whether lactate infusion in rats suppresses glycolysis preceding insulin resistance and whether lactate-induced insulin resistance is accompanied by altered insulin signaling and/or insulin-stimulated glucose transport in skeletal muscle. Hyperinsulinemic euglycemic clamps were conducted for 6 h in conscious, overnight-fasted rats with or without lactate infusion (120 micromol x kg(-1) x min(-1)) during the final 3.5 h. Lactate infusion increased plasma lactate levels about fourfold. The elevation of plasma lactate had rapid effects to suppress insulin-stimulated glycolysis, which clearly preceded its effect to decrease insulin-stimulated glucose uptake. Both submaximal and maximal insulin-stimulated glucose transport decreased 25-30% (P < 0.05) in soleus but not in epitrochlearis muscles of lactate-infused rats. Lactate infusion did not alter insulin's ability to phosphorylate the insulin receptor, the insulin receptor substrate (IRS)-1, or IRS-2 but decreased insulin's ability to stimulate IRS-1- and IRS-2-associated phosphatidylinositol 3-kinase activities and Akt/protein kinase B activity by 47, 75, and 55%, respectively (P < 0.05 for all). In conclusion, elevation of plasma lactate suppressed glycolysis before its effect on insulin-stimulated glucose uptake, consistent with the hypothesis that suppression of glucose metabolism could precede and cause insulin resistance. In addition, lactate-induced insulin resistance was associated with impaired insulin signaling and decreased insulin-stimulated glucose transport in skeletal muscle.     

Catecholamine concentrations in plasma and organs of the fetal guinea pig during normoxemia, hypoxemia, and asphyxia

To examine the responses of the sympatho-adrenal system to reduced oxygen supply we studied plasma and tissue concentrations of catecholamines during normoxemia, hypoxemia, and asphyxia in 22 fetal guinea pigs near term. Fetal blood was obtained by cardiopuncture in utero under ketamine/xylazine-anesthesia. Catecholamines were determined in plasma and tissue of 15 organs and 14 brain parts by HPLC-ECD. During normoxemia (SO2 54 +/- 4 (SE) %, pH 7.36 +/- 0.02, n = 5) plasma catecholamine levels were low (norepinephrine 447 +/- 53, epinephrine 42 +/- 12, dopamine 44 +/- 6 pg/ml). During hypoxemia (SO2 27 +/- 3%, pH 7.32 +/- 0.01, n = 6) and asphyxia (SO2 24 +/- 2%, pH 7.23 +/- 0.02, n = 11) tissue catecholamine concentrations changed with changing blood gases and with increasing plasma catecholamines. Norepinephrine concentrations increased in both skin and lung and decreased in liver, pancreas, and scalp; those of epinephrine increased in the heart, lung liver, and scalp and decreased in the adrenal. There were only minor changes in brain catecholamine concentrations except for a 50% reduction in dopamine in the caudate nucleus. Concentrations of dopamine catabolite 3,4-dihydroxyphenylacetic acid decreased in many brain parts, suggesting that cerebral catecholamine metabolism was affected by hypoxemia and asphyxia. We conclude that the sympatho-adrenal system of fetal guinea pigs near term is mature and that its stimulation by reduced fetal oxygen supply leads to changes in both plasma and tissue catecholamine concentrations.     

Blood rheology and oxygen uptake

Continuously measured oxygen uptake during constant work exercise (15' 50W) reveals increasing oxygen consumption in individuals with elevated blood viscosity parameters, indicating persistent contribution of anaerobic glycolysis during steady state exercise far below expected "anaerobic threshold". Improvement of viscosity parameters by prostaglandin E1--infusion (Prostavasin) 40 micrograms i.v., naftidrofurylhydrogenoxalat (Dusodril pi) 400 mg i.v. or hemodilution with 500 ml 6% hydroxyethylamylum MW 40000 (Onkohaes) in 5 patients results in significant reduction of this oxygen gradient in subsequent exercise test. Integrated VO2 during exercise above the mean value at rest or the quotient of VO2 during 15 min by VO2 during 30 min (including recovery time) are not differing significantly due to high variations inter- and intraindividually. Oxygen gradient during submaximal constant exercise permits direct clinical determination of microcirculatory performance in involved muscle tissue as a function of blood viscosity.     

Factors affecting hepatic glycolysis and some changes that occur during development

1. Glycolysis by the supernatant fraction of homogenates of liver from guinea pigs and rats at various stages of development (foetal, newborn and adult) has been examined in a suitably fortified medium by measurement of inorganic phosphate uptake and production of lactate and glycerol 1-phosphate. 2. Starting with glucose as substrate, two rate-determining steps in glycolysis occur at the stages of glucose phosphorylation and the phosphofructokinase reaction in liver tissue from animals of all ages. Effects of the post-natal development of glucokinase are recorded. 3. The appearance of microsomal glucose 6-phosphatase activity around birth has an effect on glycolysis owing to competition for glucose 6-phosphate. 4. A stimulating effect of the nuclear fraction, especially from foetal liver, on glycolysis by the supernatant fraction is interpreted as being due to stimulation by adenosine-triphosphatase activity at the 3-phosphoglycerate-kinase stage.     

Tissue compensatory metabolic profiles in Tilapia mossambica (Peters) on acclimation to sublethal acidic and alkaline media. Gill glycogen metabolism

Freshwater Fish, Tilapia mossambica (Peters) was acclimated to sublethal acidic and alkaline media and branchial tissue glycogen metabolism was studied. In acidic media, the glycogenolysis is elevated in the tissues and glycolysis is suppressed. In contrast, in alkaline media, the tissue glycolytic pathway is accelerated with accumulation of organic acids. In both the cases tissue had elevated G-6-PDH activity indicating stress conditions on the tissue metabolism. The tissue compensatory changes provided survival value to the fish under altered pH media.     

Pathways for glucose disposal after meal ingestion in humans

To characterize postprandial glucose disposal more completely, we used the tritiated water technique, a triple-isotope approach (intravenous [3-H(3)]glucose and [(14)C]bicarbonate and oral [6,6-(2)H(2)]glucose) and indirect calorimetry to assess splanchnic and peripheral glucose disposal, direct and indirect glucose storage, oxidative and nonoxidative glycolysis, and the glucose entering plasma via gluconeogenesis after ingestion of a meal in 11 normal volunteers. During a 6-h postprandial period, a total of approximately 98 g of glucose were disposed of. This was more than the glucose contained in the meal ( approximately 78 g) due to persistent endogenous glucose release ( approximately 21 g): splanchnic tissues initially took up approximately 23 g, and an additional approximately 75 g were removed from the systemic circulation. Direct glucose storage accounted for approximately 32 g and glycolysis for approximately 66 g (oxidative approximately 43 g and nonoxidative approximately 23 g). About 11 g of glucose appeared in plasma as a result of gluconeogenesis. If these carbons were wholly from glucose undergoing glycolysis, only approximately 12 g would be available for indirect pathway glycogen formation. Our results thus indicate that glycolysis is the main initial postprandial fate of glucose, accounting for approximately 66% of overall disposal; oxidation and storage each account for approximately 45%. The majority of glycogen is formed via the direct pathway ( approximately 73%).     

Effect of infusion of PGI-2, 6-keto-PGF-1 alpha and PGF-2 alpha on luteal function in the pregnant rat

Prostacyclin (PGI-2), 6-keto-PGF-1 alpha and PGF-2 alpha were infused continuously for 6 h into the dorsal aorta of rats 8 days pregnant. PGF-2 alpha (10 micrograms/h) significantly reduced plasma progesterone concentrations by 66% and luteal tissue concentrations of pregnenolone and progesterone by 78% and 95% respectively. Plasma concentrations of 20 alpha-dihydroprogesterone remained unchanged whilst luteal tissue concentrations rose 2-fold. Plasma progesterone concentrations were significantly reduced to 50% by PGI-2 (10 micrograms/h) but were unaffected by 6-keto-PGF-1 alpha (10 or 100 micrograms/h). Neither PGI-2 (10 micrograms/h) nor 6-keto PGF-1 alpha (10 or 100 micrograms/h) had any significant effect on plasma concentrations of 20 alpha-dihydroprogesterone or on luteal tissue concentrations of pregnenolone, progesterone or 20 alpha-dihydroprogesterone. Arterial blood pressure was unaffected by PGF-2 alpha and 6-keto-PGF-1 alpha, but was significantly reduced by PGI-2 at infusion rates greater than or equal to 60 micrograms/h.