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At least 397 records · Page 22Linked to original sources
PubMed1985

Role of renal prostaglandins in the fall in urine osmolality after papillary micropuncture.

The effect of micropuncture of the renal papilla through an intact ureter on urinary concentrating ability of rats was examined. Micropuncture of the renal papilla caused a fall in urine osmolality in the punctured kidney from 1718 +/- 106 to 1035 +/- 79 mosmol/kg X H2O. In order to investigate the role of renal prostaglandins in this process, PGE2 excretion was measured and found to increase from 63.4 +/- 14.0 to 205.5 +/- 57.1 pg/min. Urine osmolality and PGE2 excretion from the contralateral kidney were not significantly altered. In animals given meclofenamate (2 mg/kg X hr), renal PGE2 excretion was reduced to 22.3 +/- 5.1 pg/min prior to micropuncture and it remained low at 8.9 +/- 1.8 pg/min after papillary micropuncture. Meclofenamate also blocked the fall in urine osmolality caused by micropuncture of the renal papilla, with urine osmolality averaging 1940 +/- 122 before and 1782 +/- 96 mosmol/kg X H2O after the micropuncture. These results indicated that papillary micropuncture through an intact ureter increased renal PGE2 excretion and that a rise in renal production of PGE2 or some other prostanoid is associated with a fall in urine concentrating ability.

Animals↗
PubMed1986

Acetylcholine induces vasodilation and prostacyclin synthesis in rat lungs.

Acetylcholine causes pulmonary vasodilation, but its mechanism of action is unclear. We hypothesized that acetylcholine-induced pulmonary vasodilation might be associated with prostacyclin formation. Therefore, we used isolated rat lungs perfused with a recirculating cell- and plasma-free physiological salt solution to study the effect of acetylcholine infusion on pulmonary perfusion pressure, vascular responsiveness and lung prostacyclin production. Acetylcholine (20 micrograms infused over 1 minute) caused immediate vasodilation during ongoing hypoxic vasoconstriction and prolonged depression of subsequent hypoxic and angiotensin II-induced vasoconstrictions. Both effects of acetylcholine were abolished by atropine pretreatment. The prolonged acetylcholine effect, but not the immediate response, was blocked by meclofenamate, an inhibitor of cyclooxygenase. The prolonged effect, but not the immediate response, of acetylcholine was associated with an increase in perfusate 6-keto-PGF1 alpha concentration. The acetylcholine stimulated increase in 6-keto-PGF1 alpha production was inhibited by meclofenamate and by atropine. Thus, blockade of prostacyclin production corresponded with blockade of the prolonged acetylcholine effect. In conclusion, acetylcholine caused in isolated rat lungs an immediate vasodilation and a prolonged, time-dependent depression of vascular responsiveness. Whereas both acetylcholine effects were under muscarinic receptor control, only the prolonged effect depended on the cyclooxygenase pathway and, presumably, prostacyclin synthesis.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Role of prostaglandins in the cortical distribution of renal blood flow following reductions in renal perfusion pressure.

The purpose of this study was to examine the role of prostaglandins in the redistribution of renal cortical blood flow that occurs following reductions in renal perfusion pressure. The distribution of blood flow to the renal cortex was examined using radio-labeled microspheres (15 +/- 1 micron). It was found that in animals not treated with a prostaglandin synthesis inhibitor a decrease in renal perfusion pressure to the limit of renal blood flow autoregulation was associated with a decrease in fractional flow to the outer cortex (Zone I) and an increase in fractional flow to the inner cortex (Zones III and IV). A further decrease in renal perfusion pressure below the limit of autoregulation produced a further decrease in the fractional flow to Zone I and a further increase in fractional flow to Zones III and IV. In contrast, in animals treated with the prostaglandin synthesis inhibitor meclofenamate (5 mg/kg, i.v. bolus) a reduction in renal perfusion pressure to the limit of renal blood flow autoregulation produced no change in fractional blood flow to any of the 4 cortical zones. A further decrease in renal perfusion pressure, however, did produce a fall in fractional blood flow to Zone I and an increase in fractional flow to Zones III and IV. In conclusion, the results of this study indicate that within, but not below, the limit of renal blood flow autoregulation prostaglandin synthesis is an important factor in the regulation of renal cortical blood flow distribution.

Animals↗
PubMed1987

The effect of sodium meclofenamate in premenstrual asthma: a controlled clinical trial.

We speculated that changes in endogenous prostaglandin synthesis might be responsible for the syndrome of premenstrual asthma (worsening of asthma in relation to menstruation). To test our hypothesis, we compared the effects of sodium meclofenamate, a prostaglandin synthesis inhibitor, and placebo on premenstrual asthma in a 4-month, double-blind, crossover study of 17 women with asthma. Day-by-day evaluation revealed that peak expiratory flow reached a nadir during menstruation on both meclofenamate and placebo therapy and varied inversely with menstrual symptoms and asthma symptoms. Meclofenamate therapy resulted in significant improvement in peak expiratory flow during the early premenstrual period but had no treatment effect on the exacerbation of asthma during the late premenstrual period and early menstruation. The overall improvement in pulmonary function caused by meclofenamate therapy was correlated with the treatment effect on menstrual symptoms. Meclofenamate caused a small, nonsignificant decrease in use of theophylline and oral beta-agonist agents, whereas corticosteroid use increased slightly but not significantly. This study demonstrates the temporal relationship between menstrual symptoms and asthma. The study also demonstrates that inhibition of prostaglandin synthesis does not prevent exacerbation of asthma in relation to menstruation.

Adolescent↗
PubMed1980

Renal prostaglandin E2 and D2 alpha secretion and excretion in exercising conscious dogs.

Renal prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha) secretion and excretion rates were determined in dogs at rest and during various levels of treadmill exercise. Four animals were chronically instrumented to measure mean arterial pressure (MAP), heart rate (HR), left renal blood flow (RBF), and to sample renal venous (RV) blood. In four additional animals, the bladder was cannulated to enable urine collection prior to and after exercise. When compared to resting values, RV PGE2 concentrations increased by 99, 119, and 50 percent during light, moderate and heavy exercise workloads, respectively. RBF was constant during exercise and consequently renal PGE2 secretion increased as a function of RV PGE2 concentration. Similar changes were observed in PGF2 alpha in 2 dogs. When compared to resting values, excretion rates of PGE2 respectively, due to an increase in urine PGE2 and PGF2 alpha concentrations. The data demonstrate that renal PG synthesis, as evaluated by PG secretion and excretion, is increased during exercise in the dog.

Animals↗
PubMed1980

Sodium intake as a determinant of urinary prostaglandin E2 excretion.

The effect of salt-loading on urinary prostaglandin D2 (PGE2) was studied in the rat. PGE2 doubled after 4 days of gavage with 40 ml 0.9% saline. Control animals receiving 5% glucose or tap water did not show this increase. When rats were allowed ad lib saline, PGE2 increased after 2 weeks, but returned to normal at 5 weeks. This same phenomenon of increased PGE2 early in the course of salt-loading was also observed in Dahl salt-sensitive and salt-resistant rats fed an 8% salt diet. Inhibition of prostaglandin biosynthesis by meclofenamate or indomethacin did not attenuate the natriuretic effect of saline loading. We conclude: 1) Salt-related changes in PGE2 is a time-dependent phenomenon, and 2) PGE2 is not the natriuretic factor since levels normalize despite continued salt-loading, and natriuresis was unaffected by prostaglandin blockade.

Administration, Oral↗
PubMed1982

Central cardiovascular and thermal effects of prostaglandin D2 in rats.

Prostaglandin D2 (PGD2) is the most common prostaglandin type of the rat brain. Recently a neuromodulator role for PGD2 has been suggested. In the present work the central cardiovascular and thermal effects of PGD2 were studied in urethane-anaesthetised rats. When administered at the doses of 0.001-10 micrograms/rat into the lateral cerebral ventricle (i.c.v.), PGD2 slightly increased the blood pressure, heart rate and body temperature. The highest dose caused also an initial hypotensive effect. Upon intravenous injections PGD2 (0.1-10 micrograms/rat) initially decreased and then weakly increased the blood pressure but had only negligible effects on heart rate and body temperature. Central pretreatment with sodium meclofenamate or indomethacin (1 mg/rat i.c.v.) antagonised effectively all the recorded central effects of PGD2. The central cardiovascular and thermal effects of PGD2 were much weaker than those obtained earlier with other prostaglandins, such as PGF2 alpha and PGE2. Therefore, in spite of its abundance in the brain PGD2 may not be very important for the central cardiovascular and thermal regulation in the rat.

Animals↗
PubMed1984

Calcium-induced pulmonary vasodilation: modification by meclofenamate and ouabain.

Based on work with isolated arteries, we hypothesized that elevation of the extracellular calcium concentration would cause pulmonary vasodilation by stimulation of the Na+K+ATPase. If so, ouabain should inhibit the "membrane stabilizing" effect of a high calcium concentration. Addition of CaCl2 to the perfusate of rat isolated lungs to give a final concentration of 10(-2)M caused vasodilation when the lungs were vasoconstricted by KCl, angiotensin II or hypoxia. Ouabain addition to the perfusate increased pulmonary artery perfusion pressure and the magnitude of angiotensin II-induced vasoconstriction delayed vasodilation and transformed the CaCl2-induced vasodilation into rapid vasoconstriction accompanied by edema formation. Meclofenamate reduced the calcium-induced vasodilation suggesting that part of the high calcium vasodilation may be due to the action of a vasodilator prostaglandin. The vasodilation due to prostacyclin was blocked in lungs treated with ouabain. The results taken together suggest that high calcium vasodilation operates by mechanisms which may be prostaglandin-dependent and prostaglandin-independent, both of which can be blocked by ouabain.

Animals↗
PubMed1985

The role of prostaglandins in aldosterone and corticosterone secretion by isolated perfused rat zona glomerulosa cells.

The effect of PGE2 and PGA1 on aldosterone and corticosterone biosynthesis by isolated perfused rat zona glomerulosa cells has been studied. Incremental doses of each of the prostaglandins tested produced a progressive rise in aldosterone (3-4 fold increase for PGE2 and 2-3 fold increase for PGA1) and corticosterone (4-8 fold for PGE2 and 2-4 fold for PGA1). The cyclo-oxygenase inhibitors indomethacin and meclofenamate however produced no effect on basal steroidogenesis. PGE2 produced a marked potentiation of angiotensin II-induced aldosterone secretion (45.7 +/- 13.6 to 144.3 +/- 19.4 pg/ml with angiotensin II alone and 78.4 +/- 16.6 to 269.9 +/- 39.5 pg/ml with angiotensin II + PGE2). In contrast, there was no effect of PGE2 on ACTH or serotonin-induced aldosterone secretion. These data show that PGE2 and PGA1 can directly stimulate rat adrenal steroidogenesis and suggest that PGE2 may play a role in mediating angiotensin II-induced aldosterone secretion by rat zone glomerulosa cells.

Adrenal Cortex↗
PubMed1985

Interaction between prostaglandin E1 and forskolin in modulation of cyclic AMP levels in rat epididymal adipocytes.

The interaction between the diterpene, forskolin and prostaglandin E1 on cAMP levels in isolated adipocytes of the rat was examined. Various doses of Prostaglandin E1 in the presence of 1-methyl-3-isobutylxanthine (2 mM) blocked the increase in the intracellular level of cAMP elicited by forskolin (0.1 microM or 5 microM). Interestingly, in the absence of 1-methyl-3-isobutylxanthine (or an adenosine blocker), or in the presence of 1-methyl-3-isobutylxanthine (2 mM) and forskolin (30 microM), prostaglandin E1 (1 nM-100 microM) exhibited biphasic dose-response kinetics. The stimulatory effect of PGE1 (greater than 1 microM) in presence of forskolin (30 microM) may be a consequence of prostaglandin receptor modification following endogeneous release of adenosine and prostaglandins by adipocytes stimulated to high levels of cAMP accumulation due to 30 microM forskolin.

Adenosine Deaminase↗
PubMed1987

Further studies on the effects of cyclooxygenase inhibitors on compensatory renal growth.

The primary stimulus for compensatory renal growth is unknown. This process may be regulated by a circulating renotropic factor or may reflect a growth response to increased work. Prostaglandins appear to participate in compensatory renal growth as indomethacin has been shown to attenuate increases in both renal mass and function after uninephrectomy in rats. The goal of the present study was to test the effects of other cyclooxygenase inhibitors on compensatory renal growth and to evaluate the effects of indomethacin on renal growth in vitro in response to the purported renotropic factor. Both ibuprofen and meclofenamate retarded compensatory renal growth two days after uninephrectomy in rats (p less than 0.05). The addition of indomethacin to the medium of kidney slices incubating with sera from uninephrectomized rats reduced renal DNA synthesis, whereas indomethacin had no effect on renal growth when added to slices incubating with sera from intact animals. These data provide more support for an important role for prostaglandins in compensatory renal growth.

Animals↗
PubMed1985

Studies on reproduction in rats with meclofenamate sodium, a nonsteroidal anti-inflammatory agent.

Reproduction and teratology studies were performed in rats given meclofenamate sodium, a nonsteroidal anti-inflammatory agent. Dosages of 0, 3, 6, and 9 mg/kg were administered orally as dietary admixtures in the Fertility and Perinatal-Postnatal studies. In the Teratology study, dosages of 10, 12, 15, and 20 mg/kg were administered by intragastric intubation. In the Male-Fertility study no adverse effects on fertility or litter and offspring parameters were observed in two generations. In the Female-Fertility and Perinatal-Postnatal studies, maternal toxicity (death associated with intestinal ulceration and adhesions) was particularly evident during lactation. Prolonged gestation periods, decreased weanling weights, and increased weanling mortality were evident at dosages of 6 and 9 mg/kg. Increased postimplantation loss occurred at 6 and 9 mg/kg in the Term Sacrifice subgroup of the Female-Fertility study. Fertility rates were unaffected and all other litter and offspring parameters of the F1 and F2 generations appeared normal. In the Teratology study no adverse effects on embryonic or fetal development were evident at maternally toxic dosages up to 20 mg/kg.

Abnormalities, Drug-Induced↗
PubMed1988

Comparison of meclofenamate sodium and hydrocortisone for controlling the postsurgical inflammatory response in rats.

The effectiveness of meclofenamate sodium and hydrocortisone in alleviation of local postsurgical swelling and leukocytic infiltration was compared at two postsurgical intervals in 60 male Sprague-Dawley rats. Both drugs were effective at 24 hours after surgery. Ten doses of 2 mg meclofenamate sodium administered over a 5-day period were more effective in reducing leukocytic infiltration than six doses of 2 mg hydrocortisone administered over the same period. Neither the hydrocortisone nor the meclofenamate sodium at the dosage used adversely affected osteoid formation.

Animals↗
PubMed1990

Double-blind comparison of meclofenamate sodium plus codeine, meclofenamate sodium, codeine, and placebo for relief of pain following surgical removal of third molars.

A single-dose, randomized, double-blind, parallel-treatment study was performed in 200 outpatients with acute pain caused by the surgical removal of impacted third molars. Meclofenamate 100 mg plus codeine 60 mg, meclofenamate 50 mg plus codeine 30 mg, meclofenamate 100 mg, codeine 60 mg, and placebo treatment groups were compared for sum of pain intensity differences, peak pain intensity difference, sum of pain relief scores, peak pain relief, number of observations at which pain was half relieved, overall evaluation of effectiveness, and time to remedication with a backup analgesic. Meclofenamate 100 mg plus codeine 60 mg was significantly more effective (P less than .005) than codeine 60 mg for all variables except number of observations at which pain was half relieved. Both meclofenamate-codeine combinations and meclofenamate 100 mg alone were significantly more effective (P less than .005) than placebo for all variables. Eleven adverse experiences were reported in 7 patients (3.5%); the most common was somnolence in 1 patient receiving meclofenamate 100 mg plus codeine 60 mg, in 2 treated with meclofenamate 50 mg plus codeine 30 mg, and in 1 treated with codeine 60 mg.

Adolescent↗
PubMed1987

Objective changes in intrauterine pressure during placebo treatment of dysmenorrhea.

The paradoxical improvement of many subjective phenomena during placebo therapy is both well established and notorious for confounding many well designed studies. Consistently high placebo response rates of as much as 44% have been reported in subjective studies of dysmenorrhea. In an effort to evaluate the discordant role of objective uterine activity known to be associated with primary dysmenorrhea and the subjective sensation of discomfort, data from 18 patients undergoing meclofenamate therapy for primary dysmenorrhea were evaluated. In this study both the sum of pain intensity differences (SPID) and the total pain relief scores at each study time (TOTPAR) showed increases during both drug and placebo therapy with statistically significant differences favoring drug therapy. Ten percent of patients eventually reported 'complete relief' during placebo therapy. In contrast to this subjective placebo response, objective measures of intrauterine pressure showed consistent worsening in 13 out of 14 pressure parameters with 25% of patients experiencing a 2-fold or greater increase in the number of contractions while on placebo therapy. The ability to document unchanged or worsening objective parameters associated with the development of 'pain' in the face of reported subjective improvements may provide new insight into the mechanisms by which the 'placebo effect' occurs.

Clinical Trials as Topic↗
PubMed1989

Effects of non-steroidal anti-inflammatory drugs on isolated human polymorphonuclear leukocytes (PMN): chemotaxis, superoxide production, degranulation and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) receptor binding.

1. We have examined the effects of tolmetin and meclofenamate on isolated human PMN functions under FMLP stimulating conditions. 2. In a dose dependent manner, tolmetin and meclofenamate inhibited all PMN functions, except that tolmetin stimulated PMN chemotaxis. 3. Meclofenamate was much more potent than tolmetin as an inhibitory agent. 4. We also conducted competitive receptor binding assays for tolmetin, meclofenamate and ibuprofen on the FMLP receptor. 5. All three NSAID inhibited FMLP binding in a dose dependent manner with the potency order being meclofenamate greater than ibuprofen greater than tolmetin.

Adult↗
PubMed1996

Effects of verapamil on the renal actions induced by nitric oxide and prostaglandin synthesis inhibition.

This study was designed to determine the effects of a calcium antagonist (verapamil) on the renal actions induced by nitric oxide synthesis inhibition, with and without simultaneous prostaglandin synthesis inhibition. The renal effects of verapamil (2 micrograms/kg/min) were examined in anesthetized dogs before and after an increase of extracellular volume and during the reduction of nitric oxide synthesis (1 microgram/kg/min NG-nitro-L-arginine methyl ester [L-NAME]), with and without the administration of a cyclooxygenase inhibitor (5 micrograms/kg/min meclofenamate). Nitric oxide synthesis inhibition produced an increase in proximal sodium reabsorption (lithium clearance technique) and a decrease in the excretory response to volume expansion that was prevented by the administration of verapamil. The administration of a cyclooxygenase inhibitor, during nitric oxide synthesis inhibition, elicited an increase in arterial pressure, an important renal vasoconstriction, and reduced the renal excretory response to volume expansion. The antinatriuretic effect produced by the simultaneous reduction of nitric oxide and prostaglandin synthesis, before and after the volume expansion, was abolished with the verapamil infusion. However, the increase of arterial pressure and renal vasoconstriction were only partly affected by verapamil. We found that the antinatriuretic effect secondary to the reduction of nitric oxide synthesis, during an increase in extracellular volume, is prevented by the administration of verapamil. Additionally, the administration of verapamil completely prevents the antinatriuretic, but not the vasoconstrictor, effects induced by the administration of a cyclooxygenase inhibitor when nitric oxide is slightly reduced.

Animals↗