Changes In Prostaglandin Synthesis Research Articles

Effects of Dichlorodiphenyltrichloroethane on the Female Reproductive Tract Leading to Infertility and Cancer: Systematic Search and Review.

Persistent Organic Pollutants (POPs) such as dichlorodimethyltrichloroethane (DDT) are present and ubiquitous in the environment due to their resilient nature. DDT is a prevalent endocrine disruptor still found in detectable amounts in organisms and the environment even after its use was banned in the 1970s. Medline and Google Scholar were systematically searched to detect all relevant animal and human studies published in the last 20 years (January 2003 to February 2023) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. In total, 38 studies were included for qualitative synthesis. This systematic search and review indicated that exposure to DDT is associated with female reproductive health issues, such as reduced fecundability; increased risk of preterm/premature deliveries; increased periods of gestation; alterations in the synthesis of crucial reproductive hormones (Progesterone and Oxytocin) through ion imbalances and changes in prostaglandin synthesis, myometrial and stromal hypertrophy, and edema; and variations in uterine contractions through increased uterine wet weight. There was also limited evidence indicating DDT as a carcinogen sufficient to instigate reproductive cancers. However, this review only takes into account the in vitro studies that have established a possible pathway to understand how DDT impacts female infertility and leads to reproductive cancers. Links between the pathways described in various studies have been developed in this review to produce a summarized picture of how one event might lead to another. Additionally, epidemiological studies that specifically targeted the exposure to DDT of females belonging to various ethnicities have been reviewed to develop an overall picture of prevailing female reproductive health concerns in different nations.

AMPK integrates metabolite and kinase-based immunometabolic control in macrophages

ObjectivePrevious mechanistic studies on immunometabolism have focused on metabolite-based paradigms of regulation, such as itaconate. Here, we, demonstrate integration of metabolite and kinase-based immunometabolic control by AMP kinase. MethodsWe combined whole cell quantitative proteomics with gene knockout of AMPKα1. ResultsComparing macrophages with AMPKα1 catalytic subunit deletion with wild-type, inflammatory markers are largely unchanged in unstimulated cells, but with an LPS stimulus, AMPKα1 knockout leads to a striking M1 hyperpolarisation. Deletion of AMPKα1 also resulted in increased expression of rate-limiting enzymes involved in itaconate synthesis, metabolism of glucose, arginine, prostaglandins and cholesterol. Consistent with this, we observed functional changes in prostaglandin synthesis and arginine metabolism. Selective AMPKα1 activation also unlocks additional regulation of IL-6 and IL-12 in M1 macrophages. ConclusionsTogether, our results validate AMPK as a pivotal immunometabolic regulator in macrophages.

Cyclooxygenase Inhibition and Cerebrovascular Reactivity: Interaction of Aging and Aerobic Fitness

The ability of the cerebral microvessels to respond to chemical or metabolic stimuli declines with age and this change may be one mechanism through which age‐related cognitive decline occurs. Prostaglandins play an important role in the control of vascular tone, therefore changes in prostaglandin synthesis or expression may be underlying the age‐related alterations in cerebral microvascular function. Additionally, we have previously shown that aerobic fitness was associated with a decrease in cerebral microvascular function after cyclooxygenase (COX) blockade; yet this was in a small sample size of healthy older adults who were not exercise trained. Thus, the purpose of our study was to evaluate the effect of age on cerebral microvascular reactivity to hypercapnia (CVR) and to determine if habitual exercise modifies the response to COX blockade. We recruited 45 younger (YA; age = 26±1 y) and 31 older (OA; age = 63±1 y) healthy adults, including 21 sedentary YA, 24 exercising YA, 12 sedentary OA, and 19 exercising OA. Aerobic fitness (VO2 max) was measured during an incremental cycle ergometer test. Middle cerebral artery blood flow velocity (MCAv) and end‐tidal CO2 (ETCO2) were continuously recorded. CVR was calculated as the linear slope of the relationship between ETCO2 and MCAv and was assessed before and after the administration of the COX inhibitor indomethacin (INDO). The change in CVR was calculated as pre INDO CVR – post INDO CVR. There were no group differences in MCAv pre INDO (YA: 65±3 cm/s vs. OA: 59±3 cm/s; p>0.05); however, YA had higher MCAv post INDO (YA: 45±1 cm/s vs. OA: 40±2 cm/s; p<0.05). OA had significantly greater change in CVR compared with YA (2.0±0.1 cm/s/mmHg vs. 1.5±0.2 cm/s/mmHg, respectively; p<0.05). There was also a significant effect of habitual exercise, such that sedentary adults had a greater change in CVR compared with exercising adults (2.0±0.2 cm/s/mmHg vs. 1.5±0.2 cm/s/mmHg, respectively; p<0.05). In addition, there was an inverse association between VO2 max and the change in CVR in OA (r=0.42, p<0.05), but not in YA (p>0.05). Our results indicate that older adults, regardless of exercise status, rely more on COX‐derived products for cerebral microvascular responses to hypercapnia. Our results also suggest that habitual exercise may alter the contribution of COX‐derived products to cerebral blood flow regulation.Support or Funding InformationSupported by National Institute of Health grant HL118154This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Response from Sean M. Ward and Kenton M. Sanders

Response from Sean M. Ward and Kenton M. Sanders

The effect of estradiol on COX-2, EP 2, and EP 4 mRNA expression and the extracellular matrix in the cervix of the hypogonadotrophic, ovariectomized ewe

There is a degree of cervical relaxation in the ewe at estrus that is regulated by changes in prostaglandin synthesis, prostaglandin receptor expression, and changes in the cervical extracellular matrix. It is likely that these are regulated by changes in periovulatory hormones, particularly estradiol. This study determined the effect of estradiol benzoate on the mRNA expression of cyclooxygenase-2 (COX-2) and the prostaglandin E receptors EP 2 and EP 4, the concentration of cervical hyaluronan, and the proportion of smooth muscle and collagen in the cervix of the hypogonadotrophic ovariectomized ewe ( Ovis aries). Ovariectomized hypogonadotrophic ewes were given 100 μg estradiol benzoate, and their cervices were collected 0, 24, and 48 h thereafter to determine the expression of cervical COX-2, EP 2, and EP 4 mRNA by in situ hybridization, the concentration of hyaluronan by ELISA, and the proportion of smooth muscle and collagen by Masson's trichrome staining. Estradiol benzoate increased the mRNA expression of COX-2 and EP 4 within 24 h after treatment (P < 0.05), whereas EP 2 mRNA, hyaluronan, and the ratio of smooth muscle to collagen did not change within 48 h after treatment. The COX-2, EP 2, and EP 4 mRNA expression were greatest in the smooth muscle layers (P < 0.05) and least in the luminal epithelium (P < 0.05). In conclusion, we inferred that estradiol regulates cervical COX-2 and EP 4 mRNA expression and may regulate cervical relaxation via the synthesis of prostaglandin E 2 and activation of the PGE 2 receptors EP 2 and EP 4.

Inhibition of prostaglandin F 2α synthesis and oxytocin receptor by progesterone antagonists in bovine endometrial cells in vitro

Oxytocin receptor (OTR) expression is suppressed by progesterone (P4) during the luteal phase of the estrous cycle and then it increases at the time of luteolysis, but its regulation is still not completely understood. In vitro studies to determine the mechanism of action are hindered because OTR spontaneously upregulates in vitro and it is impossible to alter expression with P4 or estradiol. During recent studies examining the effect of P4 and an antagonist (mifepristone) on PG secretion, we found that mifepristone attenuated OT-stimulated PG secretion from endometrial epithelial cells. The objective of the present study was to determine, whether this effect of mifepristone was due to changes in prostaglandin synthesis and/or OTR. A time-course showed that mifepristone (5 μM) had no significant effect after 24 h but by 72 h it decreased PGF 2α secretion ( P < 0.01) and abolished the response of the cells to OT ( P < 0.01). The presence or absence of P4 did not affect the response to mifepristone. To determine the site of action of mifepristone, cells were cultured for 72 h with or without mifepristone and then COX-1 and COX-2 were measured by Western blotting and OTR was measured by saturation analysis. The results showed that mifepristone did not affect basal or PMA-stimulated expression of either COX-1 or COX-2 but did, however, decrease OTR number ( P < 0.05). These data demonstrate that OTR and the response to OT can be downregulated in endometrial epithelial cells in vitro via a mechanism involving the P4 receptor.

Gastric toxicity of racemic ketoprofen and its enantiomers in rat: oxygen radical generation and COX-expression.

The gastric toxicity of racemic-ketoprofen and its enantiomers (S(+)- and R(-)-ketoprofen), oxygen free radical generation and neutrophil infiltration in response to damage were evaluated in rats. Changes in prostaglandin synthesis, cyclooxygenase expression and glutathione metabolism were also studied. Studies were performed in Wistar rats. Drugs were given by oral administration: racemic-ketoprofen (100, 50 and 25 mg/kg body weight); S(+) and R(-)-ketoprofen (50, 25 and 12.5 mg/kg body weight). Determinations were made of gastric mucosal injury, lipid peroxidation, xanthine oxidase, myeloperoxidase and superoxide dismutase activities, glutathione levels, glutathione peroxidase and glutathione reductase activities, gastric prostaglandin synthesis (PGE2 levels) and COX-expression. Racemic-ketoprofen dose-dependently exhibited the highest toxicity. In contrast, S(+)-ketoprofen at half the dose of the racemic compound proved to be less ulcerogenic. R(-)-ketoprofen was also less ulcerogenic, but when administered as the racemate exacerbated gastric ulceration caused by S(+)-ketoprofen. Drug administration produced significant increases in lipid peroxidation levels and xanthine-oxidase and a decrease in superoxide dismutase activity. Nevertheless the racemate induced the highest disturbances in oxidative metabolism. No changes in myeloperoxidase values and glutathione metabolism were found. Cyclooxygenase-1 immunoreactivity was observed and did not differ from that in control rats. Cyclooxygenase-2 could also be expressed after treatments. R(-)-ketoprofen and S(+)-ketoprofen have a comparable gastric toxicity and they both have a better gastric toxicity profile as compared to the racemate. In addition to inhibition of prostaglandin synthesis, damage resulted in an increase of cyclooxygenase-2 protein expression. Oxygen radicals, including superoxide anions, could also be implicated.

Effects of altering dietary fatty acid composition on prostaglandin synthesis and fertility

Several studies over the past 20 years have demonstrated that subjects on diets composed of substances with high levels of n-3 polyunsaturated fatty acids (PUFAs) (e.g. fish) have a decreased incidence of heart disease. On this basis, a recent report from the Department of Health has advised UK consumers to decrease the proportion of saturated as opposed to unsaturated fats in their diet and to increase the ratio of n-3 to n-6 PUFAs. This could be achieved by altering the amounts of these constituents in milk and meat. n-3 Fatty acids can most easily be added to animal feed as either fish oil or linseed oil and can be increased in the blood and milk of ruminants following protection to avoid hydrogenation in the rumen. In western countries the ratio of consumption of n-6 to n-3 PUFAs is greater than 10 and current evidence tends to suggest that a ratio nearer 5 would be more desirable and compatible with cardiovascular well being. As fertility in the UK dairy herd is already poor, it is important to establish whether alterations in dietary n-3 and n-6 PUFAs affects herd fertility before widespread changes in animal diets are recommended. Therefore, this review considers the role played by PUFAs and eicosanoids in fertility, with particular reference to the implications for farm livestock production.The evidence reviewed shows that alteration of the concentration and ratio of n-6 and n-3 PUFAs in feeds can influence prostaglandin synthesis/metabolism in a number of mammalian systems. The changed patterns of prostaglandin synthesis can as a consequence, affect the diverse functions (e.g. hormone secretion) that are normally mediated via prostaglandins. Similarly, changes in prostaglandin synthesis effected through manipulation of PUFAs has a major bearing on fertility (as PGs affect many reproductive parameters, e.g. ovulation). Several studies in cattle and other mammals, show that feeding or infusing different types of fat with varying PUFA content to females can alter: the number and size of ovarian follicles, the ovulation rate, progesterone production by the corpus luteum, the timing of luteolysis and gestational length. In the male most recent work has focussed on sperm production and experiments in fowl have demonstrated clear effects of dietary PUFAs on both the sperm membrane phospholipid composition and on fertilizing ability.

Review of alterations in endothelial nitric oxide production in diabetes: protective role of arginine on endothelial dysfunction.

Nitric oxide release from the endothelium plays an important role in regulation of vascular tone, inhibition of both platelet and leukocyte aggregation and adhesion, and inhibition of cell proliferation. These properties suggest that the level of NO production by the endothelium may play a pivotal role in the regulation of vascular disease. Analysis using mass spectrometry has revealed that NO is produced by NOS from the terminal guanidino nitrogen of the precursor amino acid L-arginine. Thus, utilization of L-arginine and conversion to NO may establish a regulatory site in the development of endothelial dysfunction. Endothelial dysfunction is characterized by defective endothelium-dependent relaxation, and some reviews regarding endothelial dysfunction in diabetes have been published. These reviews have focused on factors that might contribute to defective relaxation, some of which will not be addressed in detail in this review. The purpose of the present review is to summarize evidence that specifically supports either decreased NO production by diabetic vascular endothelium and/or impaired NO-mediated endothelium-dependent relaxation. Second, this review provides reasonable alternatives to explain some of the controversies in this research area. Third, since there is growing evidence that arginine appears to have some benefits for diabetes-associated abnormalities, this review summarizes the current state of knowledge of effects of acute and chronic administration of L-arginine on diabetesinduced endothelial dysfunction and discusses potential NOdependent and -independent mechanisms whereby therapeutic intervention with L-arginine might benefit the diabetic endothelium.

Changes in prostaglandin synthesis and metabolism associated with labour, and the influence of dexamethasone, RU 486 and progesterone

The objective was to compare the changes in prostaglandin synthesis and metabolism occurring within the fetal membranes that are associated with the onset of parturition and to study the effect of steroid hormones on prostaglandin metabolism. A tissue explant study was made of discs of amnion and chorion obtained from 24 pregnant women at 37-42 weeks' gestation following spontaneous labour and delivery (12 women) and elective caesarean section (12 women). Significantly more prostaglandin E2 (PGE2) and PGF2 alpha were synthesized by amnion obtained following spontaneous labour than elective caesarean section. Arachidonic acid stimulated both PGE2 and PGF2 alpha synthesis by amnion in both groups. Phorbol myristoyl acetate stimulated PGE2 synthesis in both groups. There was no difference between the groups in the capacity of the chorion to metabolize prostaglandins. Mifepristone (RU 486) reduced the metabolism of added PGE2 following spontaneous labour, while dexamethasone and progesterone had no effect on prostaglandin metabolism. In conclusion, the increase in concentration of PGE2 and PGF2 alpha associated with the onset of spontaneous labour is the result of an increase in synthesis rather than a reduction in metabolism. There was no decrease in metabolism to account for the increase in prostaglandin concentrations and, with the exception of mifepristone, metabolism was not altered by the addition of steroid hormones.

Influences of oxytocin on the synthesis of prostaglandins by uterus from rats in different stages of the estrous cycle

We explored the oxytocin-prostaglandin interactions during the rat estrous cycle. The experiments were done with uterine preparations isolated from rats in different stages of the sex cycle incubated ‘in vitro’ with oxytocin (O) (50 mU/ml). We found that the effect of O on prostaglandin (PG) synthesis was associated to the sex hormones, and varied during the estrous cycle. Indeed, during the estrogenic influence (i.e. at proestrus and estrus) O diminished the synthesis of PGE 2 and with the highest estradiol concentration (i.e. during estrus) the hormone also augmented the synthesis of PGF 2α. During metestrus, no changes in PG synthesis after treatment were found. Likewise, during diestrus, when progesterone levels fall, O enhanced PGF 2α uterine synthesis. In this study an inhibitory action of O on the uterine production of 6-keto-PGF 1α at proestrus was also seen. The present results indicate that when estrogen concentration increases (during estrus) 6-keto-PGF 1α synthesis also increases. In summary, we have observed that sex hormones exert a modulating action on the influences of O on uterine PGs synthesis.

Enhanced prostaglandin synthesis as a mechanism for inhibition of melanoma cell growth by ascorbic acid

Both ascorbic acid and the 1-series prostaglandins have been reported to be important regulators of cell growth and since ascorbic acid also increases the synthesis of the 1-series prostaglandins, it is possible that the effects of ascorbic acid on cell growth might be mediated by changes in 1-series prostaglandin synthesis induced by ascorbic acid. This study attempted to examine this possible relationship. The effects of ascorbic acid, prostaglandin E 1 and the essential fatty acid precursors of the prostaglandins, linoleic acid and gamma-linolenic acid on the in vitro growth of transformed BL6 murine melanoma cells and untransformed monkey kidney (LLCMK) cells was determined. The effects of ascorbic acid addition on the growth inhibitory effect of the essential fatty acids and on the activity of delta-6-desaturase, a key enzyme in 1-series prostaglandin synthesis were also examined. Addition of ascorbic acid, prostaglandin E 1 and both essential fatty acids was found to reduce BL6 growth while PGE 1 and to a lesser extent the essential fatty acids reduced LLCMK cell growth. The growth inhibitory effect of the essential fatty acids was enhanced by ascorbic acid which was also found to stimulate delta-6-desaturase activity in BL6 cells. The growth inhibitory effect of ascorbic acid on BL6 cells may thus be mediated by changes in prostaglandin synthesis through an association with the metabolism of the essential fatty acid precursors of the prostaglandins.

Alteration of prostanoid metabolism in rats with magnesium deficiency

Plasma and tissue concentrations of prostanoids PGE 2, PGF 2α, 6-keto-PGF 1α (a stable metabolite of prostacyclin) and TXB 2 (a stable metabolite of thromboxane A 2) were measured in normal and magnesium-deficient rats. The mean values for prostanoids in plasma were significantly higher in magnesium-deficient rats than in normals (515±43 vs 296±31 pg/ml for 6-ketoPGF 1α, p<0.01, 3700±322 vs 346±33 N MI for TXB 2, p<0.001 and 1234±132 vs 434±51 pg ml for PGE 2, p<0.001). Tissue levels of prostanoids were also signifilcantly higher in magnesium-deficient rats as compared to normals. The increased synthesis of prostanoids is apparently linked to enhanced influx and translocation of Ca ++ into the cells. If the adenylate cyclase is inhibited in magnesium deficiency, the lowered c-aMP will permit a high cyclooxygenase activity and a drastic increase in TXB 2. It is possible that the changes in prostaglandin synthesis in magenesium deficiency are linked to the development of different diseases.

The effect of dietary alteration of prostaglandin synthesis on blood pressure and the reversal of hypertension in the one-kidney, one-clip rat

This study examined the effect of diet-induced changes in prostaglandin synthesis on systolic blood pressure in one-kidney, one clip (1K, 1C) hypertensive rats and on the fall in blood pressure after unclipping. It tested the hypothesis that inhibition of prostaglandin synthesis exacerbates hypertension in this model and prevents complete reversal after unclipping. Rats with sustained hypertension within 8 weeks of renal artery clipping were fed synthetic diets supplemented to 20% of total energy with either safflower oil (linoleic acid) or a mixture of cod liver oil (90%) (containing eicosapentaenoic acid) and linseed oil (10%) (containing linolenic acid) for 4 weeks. The latter oil mixture resulted in a predictable reduction in kidney PGE 2 and 6-keto PGF 1α (hydrolysis product of PGI 2), aortic 6-keto PGF 1α and serum TXB 2. However, at the end of 4 weeks dietary treatment there were no differences in systolic blood pressure between the two diet groups, and the blood pressure fall 24 hours after unclipping was similar. These findings therefore do not support a role for prostanoids in the maintenance or reversal of 1K, 1C hypertension.

Dissociation of effects of dietary fatty acids on blood pressure and prostanoid metabolism in Goldblatt hypertensive rats.

To study the influence of dietary modification of prostaglandin synthesis on blood pressure regulation, the effects of dietary enrichment with linoleic acid were compared with standard rat chow in three groups of 24 rats before and after renal artery constriction and contralateral nephrectomy. Dietary supplementation with 40 energy% sunflower seed oil or linseed oil respectively caused incorporation of linoleic or linolenic acids into tissue phospholipids. Relative to the sunflower seed oil, the linseed oil diet led to inhibition of prostanoid synthesis in kidney, serum or aorta in vitro and urine in vivo. Rats on both oil-rich diets had lower blood pressures than rats on a standard diet. Thus, partial suppression of prostaglandin synthesis did not accelerate one-kidney, one clip Goldblatt hypertension, nor did sunflower oil protect against hypertension in a way that could be specifically ascribed to changes in prostaglandin synthesis.

The [formula omitted] synthesis and degradation of prostaglandins during the development of bleomycin-induced pulmonary fibrosis in hamsters 1−3

Subsequent to optimization of conditions for enzyme assay, we examined the in vitro synthesis and degradation of prostaglandins by the lung during the devel opment of bleomycin-induced pulmonary fibrosis in hamsters. It was found that the microsomal protein content on a per lung basis was significantly increased to 144, 129, 134, and 121% of control (2.3 mg protein/lung) at 4, 7, 14 and 21 days post-treatment, respectively. The synthesis of PGD 2 was significantly elevated to 10.2, 10.8, and 12.5 moles/lung at 7, 21 and 28 days, respectively, as compared to the control value of 5.6 moles/lung. Significant increases in PGF synthesis from the control value of 3.3 moles/lung to 5.2, 8.2 and 5.5 moles/lung were found at 4, 7 and 21 days post-treatment, respectively. The synthesis of PGE 2 also showed significant increases above above the control value of 6.1 moles/lung to 10.5, 12.2 and 11.0 nmoles/lung at 7, 21 and 28 days post-treatment, respectively. Similarly, the synthesis of 6-keto-PGF was significantly increased to 7.4, 7.5 and 8.6 moles/lung at 7, 21 and 28 days post-treatment, respectively, as compared to the control value of 4.4 moles/lung. The synthesis of TxB was also significantly increased from the control value of 3.9 nmoles/lung to 7.5 and 6.4 moles/lung at 7 and 21 days post-treatment, respectively. Accompanying the increased synthesis of prostaglandins in general, the in vitro degradation of PGF was significantly increased from the control v of 71.1 nmoles/lung to 173.5, 131.7 and 143.3 nmoles/lung at at 2, 4 and 7 days after bleomycin treatment, respectively. We conclude that bleomycin-induced pulmonary fibrosis leads to changes in prostaglandin synthesis and degradation possibly as a result of an accompanying inflammatorv response and resident cellular oroliferation.

Role of prostaglandins in the control of the function of adrenal glomerulosa cells.

The role of prostaglandins in the control of aldosterone production was studied in isolated rat glomerulosa cells. Exogenous prostaglandin E2 in concentrations above 10(-9) mol/l increased the production rate of aldosterone; this effect was attenuated by the competitive antagonist, 7-oxa-13-prostynoic acid. Prostaglandin F2 alpha (10(-9)--10(-5) mol/l) failed to influence the production rate of aldosterone. The aldosterone-stimulating effect of the prostaglandin precursor, arachidonic acid (5 x 10(-4) mol/l), could not be blocked by inhibitors of prostaglandin synthesis. Basal production rate of aldosterone was not significantly influenced by non-steroidal anti-inflammatory drugs. Glomerulosa cells were stimulated by angiotensin II; this effect was not potentiated by arachidonic acid and was reduced only slightly by indomethacin. The cells were also stimulated by corticotrophin and potassium ions. The effect of these substances was not potentiated by arachidonic acid and was not inhibited by non-steroidal anti-inflammatory drugs. These results do not confirm the presumption that intra-adrenal prostaglandins play an essential role in the control of aldosterone secretion. Some effects of arachidonic acid and its antagonist, eicosatetraynoic acid, on aldosterone production are considered to be independent of changes in prostaglandin synthesis.

Alterations in prostaglandin synthesis during senescence of human lung fibroblasts

Prostaglandin (PG) synthesis by human embryo lung fibroblasts in culture was determined with increasing population doubling. These cultures synthesized PGE 2, PGF 2α, PGI 2 (prostacyclin) and TXA 2 (thromboxane A 2) in response to fetal bovine serum or ascorbic acid. Changes in prostaglandin synthesis by these cells during aging were observed in response to serum or ascorbic acid. These included a shift from the synthesis of PGI 2 and PGE 2 to TXA 2 and PGF 2α and finally to PGF 2α alone. We also observed a marked increase during aging in the release of precursor fatty acid from lipid stores upon stimulation with ascorbic acid. A parallel decrease in the ability to convert the released fatty acid to prostaglandins was detected.

Specific stimulation and inhibition of renal prostaglandin release by angiotensin analogs.

Specific stimulation and inhibition of renal prostaglandin release by angiotensin analogs.

Direct effects of prostaglandin on renal function and renin release in anesthetized dog.

Direct effects of prostaglandin on renal function and renin release in anesthetized dog.