Plasma Concentrations Of PGE2 Research Articles

Relationships between prostaglandin concentrations, a single nucleotide polymorphism in HSD17B12, and reproductive performance in dairy cows

Prostaglandins are involved in multiple processes important for fertility, with previous work in mice highlighting a potential role for the HSD17B12 gene in prostaglandin biosynthesis. This study aimed to determine the associations among circulating prostaglandin concentrations, a missense SNP in the HSD17B12 gene predicted to disrupt protein function, and fertility traits in first-lactation Holstein-Friesian dairy cows. We used a study population of approximately 500 animals specifically bred to have either a positive (POS, +5%) or negative (NEG, -5%) genetic merit for fertility (FertBV). Genotypes of a previously identified SNP (rs109711583) in HSD17B12 were determined, with 116 animals genotyped as AA, 215 genotyped as AG, and 153 genotyped as GG. Plasma concentrations of prostaglandin E2 and the PGF2α metabolite PGFM were determined at 3 time points (12 mo of age, 4 d postpartum, and 5 wk postpartum during first lactation) in a selection of animals with AA and GG genotypes from both the POS and NEG FertBV groups (n = 33-40 in each genotype for each FertBV group). Binary reproductive traits (yes or no) examined included submission for artificial breeding in the first 3 or 6 wk of the seasonal breeding period; conception to first service; conception during the first 6 wk of the breeding period; and pregnant at the end of the breeding period. Uterine health at 6 wk after calving was examined by evaluating the percentage of polymorphonuclear leukocytes following uterine cytology and by scoring vaginal discharge based on the presence of purulent material. The 3-wk submission rate was increased in animals that carried the G allele of the missense SNP in HSD17B12, but no differences were present among genotypes for 6-wk submission rate. The trait was additive, with each increase of the G allele increasing the 3-wk submission rate by 6 to 7%. We did not observe any consistent associations between SNP alleles and circulating PGE2 concentrations; however, a complex 3-way interaction among time, fertility group, and SNP allele was present for PGFM concentrations. Plasma concentrations of PGE2 were increased approximately 40% at 5 wk postpartum in animals that were submitted for breeding within 3 or 6 wk of the start of the breeding season, and in those that conceived during the first 6 wk of breeding, compared with those that did not. Plasma concentrations of PGFM were decreased approximately 20% in those animals that conceived to their first service and tended to be decreased in animals that were pregnant at the end of the breeding period, compared with those that were not. In summary, associations were observed between the SNP in HSD17B12 and submission rate by d 21 of the breeding season, as well as between circulating prostaglandin concentrations and fertility traits, but the SNP was not consistently linked to changes in prostaglandin concentrations. Thus, the association between submission rate by d 21 of the breeding season and the SNP in HSD17B12 were unlikely driven by changes in prostaglandins.

Cyclooxygenase-2 and Prostaglandin E2 are Associated with Middle Cerebral Artery Occlusion and Hemorrhage in Patients with Moyamoya Disease.

Some inflammatory proteins, such as cyclooxygenase (COX)-2 and prostaglandin (PG) E2 are hypothesized to be implicated in the development of moyamoya disease (MMD). However, the functional roles of COX-2/PGE2 in the pathogenesis of MMD remain elusive. In this study, tiny pieces of middle cerebral artery (MCA) and superficial temporal artery (STA) were surgically harvested from 18 adult MMD patients and 5 surgical control patients. The expression levels of COX-2 and microsomal prostaglandin E2 synthase-1 (mPGES-1) in the vascular walls were immunohistochemically detected. With additional 10 healthy controls, the plasma levels of PGE2 were also measured by enzyme-linked immunosorbent assay (ELISA). Obvious intimal thickening was observed in both STA and MCA of MMD patients, but not in the controls. However, the MCA had a thicker intima than the STA (P < 0.01). Although plasma concentrations of PGE2 had no differences among the MMD patients, surgical controls and healthy controls, MCA of most MMD patients (15/18, 83.3%) were stained positively for COX-2 and all patients for mPGES-1. Staining of both COX-2 and mPGES-1 was more abundant in the MCA of hemorrhagic patients than those in their ischemic counterparts (P = 0.001 and 0.029, respectively). The expression levels of COX-2 were positively correlated with those of mPGES-1 (r = 0.647, P = 0.004). Positive COX-2 and mPGES-1 expressions were detected neither in the MCA samples from the surgical controls nor in all STA specimens. Our findings indicate that COX-2/PGE2 may be associated with the MCA occlusion and the hemorrhagic stroke in patients with MMD.

Inhibition of the Prostaglandin Transporter PGT Lowers Blood Pressure in Hypertensive Rats and Mice.

Inhibiting the synthesis of endogenous prostaglandins with nonsteroidal anti-inflammatory drugs exacerbates arterial hypertension. We hypothesized that the converse, i.e., raising the level of endogenous prostaglandins, might have anti-hypertensive effects. To accomplish this, we focused on inhibiting the prostaglandin transporter PGT (SLCO2A1), which is the obligatory first step in the inactivation of several common PGs. We first examined the role of PGT in controlling arterial blood pressure blood pressure using anesthetized rats. The high-affinity PGT inhibitor T26A sensitized the ability of exogenous PGE2 to lower blood pressure, confirming both inhibition of PGT by T26A and the vasodepressor action of PGE2 T26A administered alone to anesthetized rats dose-dependently lowered blood pressure, and did so to a greater degree in spontaneously hypertensive rats than in Wistar-Kyoto control rats. In mice, T26A added chronically to the drinking water increased the urinary excretion and plasma concentration of PGE2 over several days, confirming that T26A is orally active in antagonizing PGT. T26A given orally to hypertensive mice normalized blood pressure. T26A increased urinary sodium excretion in mice and, when added to the medium bathing isolated mouse aortas, T26A increased the net release of PGE2 induced by arachidonic acid, inhibited serotonin-induced vasoconstriction, and potentiated vasodilation induced by exogenous PGE2. We conclude that pharmacologically inhibiting PGT-mediated prostaglandin metabolism lowers blood pressure, probably by prostaglandin-induced natriuresis and vasodilation. PGT is a novel therapeutic target for treating hypertension.

Effect of perioperative intravenous flurbiprofen axetil on chronic postmastectomy pain.

To explore whether perioperative intravenous flurbiprofen axetil can reduce the incidence and intensity of chronic pain for breast cancer after surgical treatment. This randomized, double-blind, controlled trial enrolled 60 patients undergoing mastectomy and axillary lymph node dissection under general anesthesia. All patients accepted Hospital Anxiety and Depression Scale (HAD) tests the day before the surgery to evaluate depression and anxiety. The patients were randomly assigned to receive either 50 mg flurbiprofen axetil intravenously 15 minutes before the surgical incision and 6 hours later (group F) or intravenous 5 mL intralipid as a control (group C). All patients received patient-controlled intravenous analgesia (PCIA) with fentanyl postoperatively. Peripheral venous blood samples were drawn before the surgery, at 4 and 24 h after the surgery to detect the plasma level of PGE2 and tumor necrosis factor-α (TNF-α). Postoperative fentanyl consumption, Numerical Rating Scale (NRS) scores and adverse effects were recorded at 2, 6, 12, 24 and 48 h after the surgery. The duration and intensity of pain were followed up by telephone at the 2nd-12th month after the surgery. The incidence of pain at 2, 4, 6, and 12 months after the breast surgery was 33%, 20%, 15%, and 10%, respectively, and the average pain score was 0.77, 0.57, 0.28, and 0.18, respectively. Compared with group C, the scores of pain in group F were significantly lower at 2, 4, 6 and 12 months postoperatively (F=7.758, P=0.007). The incidence of pain in group F was significantly lower at 2, 4 and 6 months postoperatively (P<0.05). There was no significant difference in the incidence of pain between the groups at 12 months postoperatively (P>0.05). Preoperatively and at 4 and 24 h after the surgery, there was no significant difference in the level of TNF-α between the two groups (F=0.530, P=0.470); but plasma concentration of PGE2 in group F was significantly lower than that in group C (F=5.646, P=0.021). No patients developed abnormal bleeding, peptic ulcer, impaired liver or renal function and respiratory depression. Perioperative intravenous infusion of 100 mg flurbiprofen axetil can decrease the intensity and incidence of chronic pain for breast cancer after surgical treatment.

Transforming growth factor beta(1) and prostaglandin E2 concentrations are associated with bone formation markers in ulcerative colitis patients

Osteoporosis is a significant complication of a multifactoral etiology associated with inflammatory bowel disease. The aim of study was to evaluate the relationships between bone mineral density as well as bone turnover markers and inflammatory activity modulators (i.e., PGE2 and TGFβ1) in ulcerative colitis (UC). Twenty-one active ulcerative colitis subjects and 14 healthy individuals were included into the study. We observed no significant differences in serum concentrations of osteoprotegerin and osteocalcin, as well as bone mineral density between UC patients and healthy individuals. Plasma concentrations of PGE2, TGFβ1 and TNF-α were significantly higher in UC patients than in controls. Serum osteocalcin demonstrated a positive correlation with both serum PGE2 and plasma TGFβ1. Moreover there was significant correlation between osteoprotegerin and TGFβ1 as well as serum TNF-α concentrations. In conclusion a positive association between PGE2 and TGFβ1 and bone formation markers—osteoprotegerin and osteocalcin, as well as a comparable BMD in UC patients and healthy individuals was shown. Our results may indicate that increase of PGE2 as well as TGFβ1 concentrations may play a protective role against bone loss in ulcerative colitis patients.

Continuous intrafetal infusion of prostaglandin E2 prematurely activates the hypothalamo-pituitary-adrenal axis and induces parturition in sheep.

This study has investigated the effect of continuous intrafetal infusion of PGE2 or saline on hormone concentrations and the length of gestation in sheep. Fetal and maternal vascular catheters were surgically implanted at 112.3 +/- 1.3 days (n = 10), and the infusions were started at 121 +/- 1.2 days of gestation (term = 147). Fetuses were infused with either PGE2 (n = 5; 2 micrograms/min for 48 h and then increased to 4 micrograms/min for the remainder of the experiment) or the vehicle solution (n = 5; sterile isotonic saline) via the fetal carotid artery. In the PGE2-infused group, fetal and maternal plasma PGE2 concentrations increased (P < 0.001) after the change to the higher dose rate (4 micrograms/min) and remained elevated, fetal plasma immunoreactive ACTH (ir-ACTH) concentrations dramatically increased after the start of the infusion being maximal at 11 h before decreasing to match concentrations exhibited by the saline-infused group. Fetal plasma cortisol concentrations increased after the start of the PGE2 infusion (P = 0.05) and increased further after the change to the higher dose rate of 4 micrograms/min (P < 0.001). Concentrations of PGE2, ir-ACTH, and cortisol in the saline-infused group did not change until labor. Plasma concentrations of PGE2 (P < 0.001) and ir-ACTH (P < 0.005) increased on the day of labor in both treatment groups, and fetal cortisol concentrations increased (P < 0.001) in both groups in the last few days before labor. The proportion of low molecular weight ir-ACTH in the plasma of PGE2-infused fetuses was significantly higher than that of saline-infused fetuses (P < 0.001) during the first 15 days of infusion. In the saline-infused group, the proportion of low molecular weight ir-ACTH increased in the last few days before labour (P = 0.001), whereas no change was seen in PGE2-infused fetuses at this time. Maternal plasma progesterone concentrations decreased in both groups in the last few days before labor (P < 0.001). Fetuses infused with PGE2 delivered at 138.4 +/- 2.1 days, whereas control fetuses infused with saline delivered at 148.2 +/- 0.5 days (P < 0.001). The spontaneous increase in PGE2 preceding normal labor may thus play an important role in activation and maturation of the hypothalamic-pituitary-adrenal axis in fetal sheep.

Continuous intrafetal infusion of prostaglandin E2 prematurely activates the hypothalamo-pituitary-adrenal axis and induces parturition in sheep

This study has investigated the effect of continuous intrafetal infusion of PGE2 or saline on hormone concentrations and the length of gestation in sheep. Fetal and maternal vascular catheters were surgically implanted at 112.3 +/- 1.3 days (n = 10), and the infusions were started at 121 +/- 1.2 days of gestation (term = 147). Fetuses were infused with either PGE2 (n = 5; 2 micrograms/min for 48 h and then increased to 4 micrograms/min for the remainder of the experiment) or the vehicle solution (n = 5; sterile isotonic saline) via the fetal carotid artery. In the PGE2-infused group, fetal and maternal plasma PGE2 concentrations increased (P < 0.001) after the change to the higher dose rate (4 micrograms/min) and remained elevated, fetal plasma immunoreactive ACTH (ir-ACTH) concentrations dramatically increased after the start of the infusion being maximal at 11 h before decreasing to match concentrations exhibited by the saline-infused group. Fetal plasma cortisol concentrations increased after the start of the PGE2 infusion (P = 0.05) and increased further after the change to the higher dose rate of 4 micrograms/min (P < 0.001). Concentrations of PGE2, ir-ACTH, and cortisol in the saline-infused group did not change until labor. Plasma concentrations of PGE2 (P < 0.001) and ir-ACTH (P < 0.005) increased on the day of labor in both treatment groups, and fetal cortisol concentrations increased (P < 0.001) in both groups in the last few days before labor. The proportion of low molecular weight ir-ACTH in the plasma of PGE2-infused fetuses was significantly higher than that of saline-infused fetuses (P < 0.001) during the first 15 days of infusion. In the saline-infused group, the proportion of low molecular weight ir-ACTH increased in the last few days before labour (P = 0.001), whereas no change was seen in PGE2-infused fetuses at this time. Maternal plasma progesterone concentrations decreased in both groups in the last few days before labor (P < 0.001). Fetuses infused with PGE2 delivered at 138.4 +/- 2.1 days, whereas control fetuses infused with saline delivered at 148.2 +/- 0.5 days (P < 0.001). The spontaneous increase in PGE2 preceding normal labor may thus play an important role in activation and maturation of the hypothalamic-pituitary-adrenal axis in fetal sheep.

Evening primrose oil and olive oil in treatment of rheumatoid arthritis.

The effects of 10 ml of evening primrose oil or olive oil, administered twice daily for 12 weeks, on clinical and laboratory signs and on plasma prostaglandins were studied in 18 patients with rheumatoid arthritis. The plasma concentration of PGE2 decreased and that of TxB2 increased in both treatment groups, but no significant improvement could be seen in either group.

Relevance of Prostaglandins in True Menstrual Migraine

Eighteen patients suffering from true menstrual migraine and 12 control subjects were studied. We evaluated in different phases of the menstrual cycle and during the migraine crisis the peripheral plasma concentrations of 6-keto-PGF1 alpha (the stable metabolite of PGI2), thromboxane B2 (the stable metabolite of thromboxane A2), PGF2 alpha and PGE2. The mean values of 6-keto-PGF1 alpha in menstrual migraine sufferers are lower than in normal women throughout the whole cycle. The difference between the trends observed in the two groups is statistically significant (p less than 0.05). The plasma levels of TXB2 and of PGF2 alpha are similar in the two groups investigated, both in basal conditions and during the attack. The plasma concentrations of PGE2 are slightly lower in migraineurs in basal conditions than in normals. However, during the crisis they increase significantly (p less than 0.05). In conclusion, among all the parameters considered, PGE2 seems to play the most important role during the pain phase of the attack. The results of the present study suggest that a deficit of PGI2, one of the most important protecting agents against ischemia, might be a typical feature of menstrual migraine and might cause in these patients a vascular hypersensitivity to different ischemic stimuli.

Prostaglandin E2 causes hypoventilation and apnea in newborn lambs.

To test the hypothesis that prostaglandin (PG) E2 is a respiratory depressant in the newborn lamb, 12 chronically catheterized, unanesthetized lambs (age 2-6 days) were infused with progressively increasing doses of PGE2 (0.1, 0.5, 1.0, and 5.0 micrograms.kg-1.min-1; 30 min for each dose) into the ascending aorta. PGE2 caused significant progressive decreases in ventilation (due to decreased tidal volume and breathing rate), heart rate, blood pressure, and percent of the time spent in low-voltage electrocortical activity (LVA). PGE2 also caused respiratory acidosis, hypoxemia, and increased frequency and duration of apneic events (greater than 3 s). During the infusion there was a dose-related increase in plasma concentration of PGE2. At 30 min postinfusion, all measured variables showed recovery, although arterial pH, CO2 tension, and plasma PGE2 remained significantly different from control values, and the percent time in LVA was even higher than during control. Infusion of the vehicle alone (n = 5) caused no significant changes in any of the measured variables. The results, taken in combination with previous fetal studies, indicate that PGE2 has marked inhibitory effects on breathing movements both before and after birth.

Effect of nafazatrom and indomethacin on pulmonary removal of prostaglandin E1 after endotoxin in rabbits.

1 We compared the effects of endotoxin on pulmonary prostaglandin E1 (PGE1) removal in groups of rabbits pretreated with the cyclo-oxygenase inhibitor, indomethacin, or nafazatrom (Bay g 6575), which has been shown to increase plasma prostacyclin concentrations. 2 In untreated animals, endotoxin transiently decreased pulmonary removal of [3H]-PGE1, caused pulmonary hypertension, systemic hypotension and increased plasma concentrations of PGE2 and 6-keto-PGF1 alpha. 3 Indomethacin pretreatment prevented the transient decrease in pulmonary removal of [3H]-PGE1 in response to endotoxin, prevented the haemodynamic effects and inhibited prostaglandin synthesis. Pretreatment with nafazatrom did not affect the decreased pulmonary removal of [3H]-PGE1, exacerbated the haemodynamic response, reduced survival and potentiated the increase in circulating 6-keto-PGF1 alpha. 4 We conclude that indomethacin acts to prevent the depression of pulmonary [3H]-PGE1 removal by eliminating surface area changes associated with endotoxin-induced pulmonary vasoconstriction. 5 These data suggest that nafazatrom treatment results in exacerbation of the endotoxin-induced systemic hypotension presumably due to its effect on increased plasma prostacyclin during the later phase of endotoxaemia.

Liposyn infusion increases plasma prostaglandin concentrations.

To determine whether Liposyn infusion results in increased plasma prostaglandin (PG) concentrations, the following study was performed in 33 adult rabbits with chronically implanted arterial and venous catheters. Plasma PG concentrations were determined by radioimmunoassay for two vasodilators, PGE2 and PGI2 (as measured by its metabolite 6-keto-PGF1 alpha), and two vasoconstrictors, thromboxane (TX) A2 and PGF2 alpha, as measured by their metabolites TXB2 and PGF2 alpha-M, respectively. A 1-hour infusion of Liposyn at 4 ml per kg resulted in statistically significant increases in arterial and venous concentrations of PGE2 and 6-keto-PGF1 alpha (p less than 0.001) and of TXB2 (p less than 0.04). There were no significant changes in PGF2 alpha-M plasma concentrations. Liposyn infusion also resulted in a small but statistically significant increase in PaO2 of 4.7 +/- 1.5 torr (p less than 0.01). It is concluded that Liposyn infusion results in statistically significant increases in plasma concentrations of PGE2, 6-keto-PGF1 alpha, and TXB2.

Determination of peripheral plasma prostanoid concentration: an unreliable index of 'in vivo' prostanoid activity.

Plasma concentrations of PGE2, PGF2 alpha, 6-keto-PGF1 alpha and TxB2 were determined in 4 healthy volunteers by gas chromatography-negative ion chemical ionization mass spectrometry. TxB2 concentrations in all volunteers increased with time during blood collection, increases occurred more sporadically in the case of PGE2, PGF2 alpha and 6-keto-PGF1 alpha. Rapid changes in plasma prostanoid concentrations within a sampling series were unpredictable and were inexplicable. The measured plasma prostanoid concentrations apparently depended on the sampling conditions, which could not be adequately standardized and controlled. However, very short term changes in plasma prostanoid levels cannot be excluded.

Role of PGE2 in the modulation of the adrenergic response in man.

The influence of sympathetic stimulation (SS) (achieved by 2 min cold application) on the plasma concentration of PGE2, PGF2 alpha (radioimmunoassay), noradrenaline (NA) and adrenaline (A) (radioenzymatic assay) and on forearm vascular resistance (indirect measurement, FVR) was studied in 16 healthy volunteers before and after cyclooxygenase inhibition by indomethacin (200 mg per day orally for 3 days) and lysine acetylsalicylate (corresponding to 10 mg X kg-1 of acetylsalicylic acid -ASA- iv). SS induced a sharp increase in PGE2 (from 8.1 +/- 4.3 pg X ml-1 before SS to 23.9 +/- 6.5, P less than 0.001 2 min after the beginning of SS and then to 18.9 +/- 10.2, P less than 0.001 to 8.4 +/- 3.9, NS, 4 and 12 min respectively after the beginning of SS). Plasma levels of PGF2 alpha remained undetectable both before and after SS. The increase in PGE2 was associated with a simultaneous increase in NA (from 13.4 +/- 24.2 to 204.1 +/- 67.2 pg X ml-1, P less than 0.001 during SS and 140.6 +/- 39.5, NS at the end of the experiment), whereas A did not vary significantly. FVR increased significantly only during SS. ASA did not affect PGE2 and NA plasma levels at rest or after SS. No PGE2 was detected during IND administration either before or after SS. IND significantly increased NA plasma concentration at the observation made 12 min after the beginning of SS (185.2 +/- 64.3 pg X ml-1 vs basal values of 135.9 +/- 46.2 pg X ml-1, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in plasma concentrations of prostaglandins and plasma angiotensin-converting enzyme during bleomycin-induced lung fibrosis in hamsters.

The effects of intratracheal administration of bleomycin on plasma concentrations of PGE2, PGF2α, TxB2, and 6-keto-PGF1α, total amount of lung collagen, and plasma angiotensin-converting enzyme (ACE) were studied in hamsters. The plasma concentrations of PGE2 were significantly increased from the control value of 462 pg/ml to 720, 665, and 592 pg/ml at 4, 7, and 14 days after bleomycin treatment, respectively. The plasma concentrations of PGF2α did not change at any time after treatment. The plasma concentrations of TxB2 were significantly increased from the control value of 187 pg/ml to 267, 272, 307, 257, and 253 pg/ml at 2, 4, 7, 14, and 21 days after bleomycin treatments, respectively, but decreased to 108.7 pg/ml at 28 days. Similarly, the concentrations of 6-keto-PGF1α were significantly increased from the control value of 588 pg/ml to 866, 1,186, and 963 pg/ml at 4, 14, and 21 days after bleomycin treatment, respectively, but decreased to 297.5 pg/ml at 28 days. The amount of total collagen in lung was significantly increased from the control value of 231.1 μg hydroxyproline/lung to 277.4, 481.1, 399.0, and 396.5 μg/lung at 7, 14, 21, and 28 days after bleomycin treatment, respectively. The plasma ACE was generally decreased at all time points with significant decreases occurring at 4 and 7 days after treatment. A positive correlation between the amount of total lung collagen and plasma concentrations of 6-keto-PGF1α and a negative correlation between the plasma ACE and the plasma concentrations of TxB2 were evident in hamsters treated with bleomycin. We concluded from the findings of the present study that increased circulating levels of PGE2, TxB2, and 6-keto-PGF1α are involved in bleomycin-induced lung fibrosis.

Role of the prostaglandin in norepinephrine release during augmented renal sympathetic nerve activity in the dog.

To determine the role of the prostaglandins on renal norepinephrine release, the effect of inhibition of prostaglandin synthesis was examined in anesthetized dogs during reflex activation of the renal adrenergic nerves. Hypotension increased the renal vein plasma concentrations of norepinephrine from 380 +/- 59 to 608 +/- 106 pg/ml (mean +/- SEM; P less than 0.01) and of PGE2 from 55 +/- 7 to 81 +/- 41 pg/ml (P less than 0.05). Subsequent administration of indomethacin or meclofenamate lowered the renal venous concentration of PGE2 to 26 +/- 3 pg/ml (P less than 0.01), had no significant effect on the norepinephrine concentration (620 +/- 89 pg/ml). Administration of indomethacin or meclofenamate to dogs with sodium depletion lowered renal venin plasma concentration of PGE2 from 108 +/- 40 to 20 +/- 3 pg/ml (0.05 less than P less than 0.1) but had no effect on the renal venous norepinephrine concentration (475 +/- 50 vs. 397 +/- 46 pg/ml). In dogs fed a normal salt diet, inflation of a balloon placed in the thoracic inferior vena cava lowered cardiac output and increased the renal venous concentrations of norepinephrine from 212 +/- 60 to 496 +/- 112 pg/ml (P less than 0.01) and of PGE2 from 28 +/- 5 to 96 +/- 18 pg/ml (P less than 0.01). Subsequent administration of indomethacin lowered the renal venous concentration of PGE2 to 16 +/- 5 pg/ml (P less than 0.01), but had no significant effect on the concentration of norepinephrine (548 +/- 91 pg/ml). During the three experimental conditions examined, renal blood flow was lowered by inhibition of prostaglandin synthesis. These results in the dog suggest that the attenuating effect that prostaglandins exert on the renal vascular action of the adrenergic nerves is not due to inhibition of norepinephrine release.