PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Meclofenamic Acid”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 433 records · Page 24Linked to original sources
PubMed2003

Coronary effects of vasopressin during partial ischemia and reperfusion in anesthetized goats. Role of nitric oxide and prostanoids.

To examine the coronary effects of arginine-vasopressin and its interaction with nitric oxide and prostanoids during partial ischemia and reperfusion, left circumflex coronary artery flow was electromagnetically measured and partial occlusion of this artery was induced for 60 min, followed by reperfusion in anesthetized goats (seven non-treated, six treated with N(W)-nitro-L-arginine methyl esther (L-NAME) and five with meclofenamate). During partial coronary occlusion, coronary vascular conductance decreased by 20-31% (P<0.01), and the coronary vasodilatation in response to acetylcholine (3-100 ng) and sodium nitroprusside (1-10 microg) was much reduced in every case; the vasoconstriction in response to arginine-vasopressin (0.03-0.3 microg) was attenuated in non-treated animals; this attenuation was reversed by L-NAME and was accentuated by meclofenamate. At 30 min of reperfusion, coronary vascular conductance remained decreased by 11-25% (P<0.05 or P<0.01), and the vasodilatation in response to acetylcholine and sodium nitroprusside as well as the vasoconstriction with arginine-vasopressin was as in the control and comparable in the three groups of animals. These results suggest: (1) that, during ischemia, the coronary vasodilator reserve is greatly reduced and the vasoconstriction with arginine-vasopressin is attenuated, with preservation of the modulatory role of nitric oxide and probable involvement of vasoconstrictor prostanoids in this vasoconstriction; and (2) that, during reperfusion, the coronary vasodilator reserve and the coronary reactivity to acetylcholine and arginine-vasopressin recover, but the modulatory role of nitric oxide in this reactivity may be attenuated.

Acetylcholine↗
PubMed1998

Coronary vasoconstriction produced by vasopressin in anesthetized goats. Role of vasopressin V1 and V2 receptors and nitric oxide.

To examine the role of vasopressin V1 and V2 receptors, nitric oxide and prostanoids in the coronary vascular effects of [Arg8]vasopressin, coronary blood flow was measured with an electromagnetic flow transducer placed around the left circumflex (23 goats) or anterior descending (11 goats) coronary artery and vasopressin (0.03-1 microg) was intracoronarily injected in 34 anesthetized, open-chest goats. Basal mean values for coronary blood flow, mean systemic arterial pressure and heart rate, were 34 +/- 2.38 ml/min, 89 +/- 3.34 mmHg and 80 +/- 3.06 beats/min, respectively. Vasopressin produced dose-dependent decreases in coronary blood flow and the maximal reduction of this flow, attained with 1 microg of vasopressin, was 14 +/- 1.49 ml/min (42 +/- 2.64% of basal flow) (P < 0.01). Desmopressin (0.03-1 microg; 8 goats) did not affect significantly coronary blood flow. The intracoronary infusion of the antagonist for vasopressin V1 receptors d(CH2)5Tyr (Me) arginine vasopressin (2 microg/min per kg, 6 animals) significantly diminished the effects of vasopressin on coronary blood flow (the effects of 1 microg of vasopressin were reduced by 28%, P < 0.05). The mixed antagonist for vasopressin V1 and V2 receptors desGly-d(CH2)5-D-Tyr(Et)Val arginine vasopressin (0.2, 0.7 and 2 microg/min per kg, 9 animals) decreased in a dose-dependent manner the effects of vasopressin on coronary blood flow (the effects of 1 microg of vasopressin were decreased by 61% with 2 microg/min per kg, P < 0.01). Intracoronary infusion of saline (vehicle, 3 goats) did not change the effects of vasopressin on coronary blood flow. Intravenous administration of the inhibitor of nitric oxide synthesis N-omega-nitro-L-arginine methyl ester (L-NAME, 47 mg/kg, 9 animals) decreased resting coronary blood flow by 10% (P < 0.01) and augmented mean systemic arterial pressure by 20% (P < 0.01), without changing heart rate. During this treatment the reduction in coronary blood flow produced by vasopressin was higher than under control (the effects of 1 microg of vasopressin were increased by 28%, P < 0.01). Intravenous administration of the inhibitor of cyclooxygenase, meclofenamate (5 mg/kg, 7 animals), neither modified resting coronary blood flow, arterial pressure and heart rate nor the effects of vasopressin on this flow. These data indicate that vasopressin produces marked coronary vasoconstriction and suggest that: (a) it may be mediated by vasopressin V1 receptors, without involvement of vasopressin V2 receptors, (b) it is probably inhibited by nitric oxide under normal conditions and (c) it may be not modulated by prostanoids.

Anesthesia, General↗
PubMed1998

R-(-)-alpha-methyl-histamine has nitric oxide-mediated vasodilator activity in the mesenteric vascular bed of the cat.

Responses to the histamine H3 receptor agonist R-(-)-alpha-methyl-histamine were investigated in the mesenteric vascular bed of the cat under constant-flow conditions. Injections of R-(-)-alpha-methyl-histamine and histamine caused dose-related decreases in mesenteric perfusion pressure with R-(-)-alpha-methyl-histamine being 1000-fold less potent than histamine when doses were compared on a nmol basis to take molecular weight into account. Responses to R-(-)-alpha-methyl-histamine were not altered by histamine H1 or H2 receptor antagonists at a time when responses to histamine were significantly reduced. The histamine H3 receptor antagonist thioperamide reduced responses to R-(-)-alpha-methyl-histamine but was without effect on responses to histamine [6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoro-methylphenyl)heptaneca rdoxamide dimaleate] (HTMT), or dimaprit. These data suggest the presence of histamine H1, H2 and H3 receptors mediating vasodilation in the mesenteric vascular bed. Responses to R-(-)-alpha-methyl-histamine and histamine were reduced by the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) but were not altered by the cyclooxygenase inhibitor meclofenamate, the alpha-adrenoceptor blocker phentolamine, or adrenergic nerve terminal depleting agent reserpine. The present data suggest that histamine H3 receptors mediating vasodilation are present in the mesenteric vascular bed and that responses are mediated by the release of nitric oxide but not vasodilator prostaglandins or an effect on the adrenergic nervous system. These results indicate that vasodilator responses to histamine involve the activation of histamine H1 and H2 receptors and the release of nitric oxide in the mesenteric vascular bed of the cat.

Animals↗
PubMed1997

In vitro relaxation of dog cerebral veins in response to histamine is mediated by histamine H2 receptors.

There is little information on the histamine receptor mechanisms involved in cerebral venodilation, thus the role of histamine present in human cerebrospinal fluid is difficult to assess. In isolated canine pial veins, concentration-response curves to histamine (10[-7]-10[-3] M), the histamine H1 receptor agonist, 2-pyridylethylamine (10[-6]-10[-2] M), the histamine H2 receptor agonist, dimaprit (S-(3-dimethylaminopropyl) isothiourea dihydrochloride, 10[-6]-10[-2] M), and the histamine H3 receptor agonist, imetit (S-[2-(1 midazol-4-yl)ethyl]isothiourea dihydrobromide, 10[-7]-10[-3] M) were isometrically determined. In resting veins, histamine, 2-pyridylethylamine and dimaprit had no significant effect, whereas in endothelin-1-precontracted veins, these drugs produced concentration-dependent relaxation (Emax in % of active tone and pD2 were: for histamine, 72 +/- 6 and 5.36 +/- 0.09; for 2-pyridylethylamine, 59 +/- 5 and 3.28 +/- 0.05; for dimaprit, 65 +/- 7 and 4.81 +/- 0.10, respectively). The relaxations in response to histamine and dimaprit were competitively antagonized by the histamine H2 receptor antagonist, cimetidine (3 x 10[-6]-10[-4] M) (pA2 = 6.07 +/- 0.03 for histamine, and 6.09 +/- 0.07 for dimaprit), but were not affected by the histamine H1 receptor antagonist, chlorpheniramine (10[-6] M) or the histamine H3 receptor antagonist, thioperamide (N-cyclohexyl-4-(1-H-imidazol-4-yl)-1-piperidine-carbothioamide maleate, 10[-6] M). The relaxation in response to 2-pyridylethylamine was inhibited by cimetidine (10[-5] M), but not by chlorpheniramine (10[-6] M). Imetit produced a small contraction in resting veins (14 +/- 4 mg) and precontracted veins (20 +/- 3 mg), which was not modified by thioperamide (10[-6] M). The relaxation of veins in response to histamine was not modified by endothelium removal, nor by the inhibitor of nitric oxide synthase, N(G)-nitro-L-arginine methyl ester (10[-4] M), or the cyclooxygenase inhibitor, meclofenamate (10[-5] M). Therefore, in pial veins: (1) histamine produces relaxation by activation of histamine H2 receptors, probably located in the smooth musculature, with no participation of histamine H1 and H3 receptors, and (2) endothelium, nitric oxide and prostanoids are probably not involved in the relaxation in response to histamine.

Animals↗
PubMed1998

In vivo and in vitro action of endothelin-1 on goat cerebrovascular bed.

This study concerned the effects and mechanisms of action of endothelin-1 on the cerebral circulation. Cerebral blood flow was electromagnetically measured in awake goats. Endothelin-1 (0.01-0.3 nmol) produced dose-dependent decreases in this flow (maximal reduction = 34%) and increases in cerebrovascular resistance (maximal increase = 74%) (P < 0.01). IRL 1620 (Suc-[Glu9, Ala11,15]endothelin-1-(8-21), agonist for endothelin ET(B) receptors, 0.01-0.3 nmol) slightly decreased cerebral blood flow. The effects of endothelin-1, but not those of IRL 1620, on cerebral blood flow were diminished by 50% during infusion of the antagonist for endothelin ET(A) receptors, BQ-123 (cyclo-(D-Asp-Pro-D-Val-Leu-Trp), 2 nmol min(-1)), but not affected during infusion of the antagonist for endothelin ET(B) receptors, BQ-788 (N-[N-[N-[(2,6-dimethyl-1-piperidinyl)carbonyl]-4-methyl-L-Leucyl-1-(met hoxycarbonyl)-D-tryptophyl]-Dnorleucine monosodium), 2 nmol min(-1)). Intravenous administration of NW-nitro-L-arginine methyl ester (L-NAME, 47 mg kg(-1)) or NW-nitro-L-arginine (L-NNA, 47 mg kg(-1)) reduced basal cerebral blood flow by 39 and 33%, increased cerebrovascular resistance by 108 and 98% and mean arterial pressure by 23 and 17%, and decreased heart rate by 27 and 25%, respectively (all at least P < 0.05). The increases in cerebrovascular resistance (as absolute values) induced by endothelin-1 were not affected during either L-NAME or L-NNA (as absolute values and percentages). Intravenous administration of meclofenamate (5 mg kg(-1)) did not change the cerebrovascular effects of endothelin-1 and IRL 1620. In isolated goat cerebral arteries under control, resting conditions, endothelin-1 (10(-11)-10(-7) M) induced concentration-dependent contractions (EC50 = 4.78 X 10(-9) M; maximal contraction = 3177+/-129 mg), whereas IRL 1620 (10(-11)-10(-7) M) produced no effect. This contraction produced by endothelin-1 was competitively blocked by BQ-123 (10(-7)-3 X 10(-6) M), and was not affected by BQ-788 (10(-6) and 10(-5) M). L-NAME (10(-4) M), meclofenamate (10(-5) M), indomethacin (10(-5) M), L-NAME (10(-4) M) plus meclofenamate (10(-5) M) and phosphoramidon (10(-4) M) did not affect the contraction in response to endothelin-1. Endothelium removal increased the response to endothelin-1, as well as the BQ-123 antagonism against endothelin-1 (pA2 values, 7.62 vs. 6.88; P < 0.01). In both intact and de-endothelized arteries precontracted with prostaglandin F2alpha endothelin-1 induced a further contraction, and IRL 1620 caused no effect. These results suggest that: (1) endothelin-1 produces cerebral vasoconstriction by activating endothelin ET(A) receptors probably located in smooth muscle; (2) endothelin ET(B) receptors, nitric oxide and prostanoids might be not involved in the cerebrovascular action of endothelin-1, and (3) endothelium removal may increase cerebrovascular reactivity by increasing sensitivity of endothelin ET(A) receptors to endothelin-1.

Animals↗
PubMed1999

Delayed protection against ventricular arrhythmias by monophosphoryl lipid-A in a canine model of ischaemia and reperfusion.

Bacterial endotoxin reduces the severity of ventricular arrhythmias which occur when a coronary artery is occluded several hours later. We have now examined in anaesthetised dogs the effects on ischaemia and reperfusion-induced arrhythmias, of a non-toxic derivative component of the endotoxin molecule of the lipid-A (monophosphoryl lipid-A). This was given intravenously, in doses of 10 and 100 microg kg(-1), 24 h prior to coronary artery occlusion. Arrhythmia severity was markedly reduced by monophosphoryl lipid-A. During ischaemia, ventricular premature beats were reduced from 315+/-84 in the vehicle controls to 89+/-60 (with the lower dose of monophosphoryl lipid-A) and 53+/-23 (P<0.05) with the higher dose. The incidence of ventricular tachycardia was reduced from 75% to 25% (P<0.05) and 31% (P<0.05), and the number of episodes of ventricular tachycardia from 13.4+/-4.9 per dog to 1.1+/-1.1 (P<0.05) and 1. 2+/-0.9 (P<0.05) after doses of 10 and 100 microg kg(-1), respectively. The incidence of ventricular fibrillation during occlusion and reperfusion in the control group was 96% (15/16), i.e., only 6% (1/16) dogs survived the combined ischaemia-reperfusion insult. Monophosphoryl lipid-A (100 microg kg(-1)) significantly reduced the incidence of occlusion-induced ventricular fibrillation (from 50% to 7%; P<0.05), and increased survival following reperfusion to 54% (P<0.05). Monophosphoryl lipid-A also significantly reduced ischaemia severity as assessed from ST-segment elevation recorded from epicardial electrodes as well as the degree of inhomogeneity of electrical activation within the ischaemia area. There were no haemodynamic differences prior to coronary occlusion between vehicle controls and monophosphoryl lipid-A-treated dogs. These results demonstrate that monophosphoryl lipid-A reduces arrhythmia severity 24 h after administration. Although the precise mechanisms are still unclear, there is some evidence that nitric oxide and prostanoids (most likely prostacyclin) may be involved because the dual inhibition of nitric oxide synthase and cyclooxygenase enzymes by administration of aminoguanidine and meclofenamate abolished the marked antiarrhythmic protection resulted from monophosphoryl lipid-A treatment 24 h previously.

Animals↗
PubMed1977

Effect of inhibitors of prostaglandin synthesis and metabolism on ovum transport in the rabbit.

Several drugs known to affect prostaglandin synthesis, release, or metabolism have been tested for their effects on ovum transport in the rabbit after systemic or local administration. Acceleration of transport was obtained with several drugs; among the most effective were benzydamine, a blocker of thromboxane production, and L11204, an inhibitor of prostaglandin metabolism.

Animals↗
PubMed1990

Nonsteroidal anti-inflammatory drugs in the treatment of eosinophilic cystitis.

A 30-year-old white woman with urinary frequency, left costovertebral angle pain and hematuria had left hydronephrosis, a marked decrease in bladder capacity and severe eosinophilic cystitis on biopsy. She was treated with a nonsteroidal anti-inflammatory drug and an antihistamine, with a dramatic, complete and rapid recovery. The nonsteroidal anti-inflammatory drug was believed to have been responsible for the favorable outcome, since antihistamines have not produced reliable benefits in this disease. Nonsteroidal anti-inflammatory drugs are recommended in cases of eosinophilic cystitis.

Adult↗
PubMed2001

Differential responses to ATPgammaS in the mesenteric and hindlimb vascular bed of the cat.

The mechanism by which the purinergic agonist adenosine 5'-O-(3 thiotriphosphate) (ATPgammaS) decreases vascular resistance was investigated in the mesenteric and hindlimb vascular beds of the cat. Injections of ATPgammaS into the hindlimb perfusion circuit elicited dose-dependent decreases in perfusion pressure while injections into the mesenteric circuit produced a biphasic response with an initial vasopressor response followed by a vasodepressor response. In the mesenteric vascular bed the pressor response to ATPgammaS was blocked by a P2X1 receptor antagonist. Also an inhibitor of nitric oxide synthase enhanced the vasoconstrictive responses to ATPgammaS. However, the vasodepressor response in the mesenteric bed was not altered by the adminstration of an alpha adrenergic receptor antagonist, a cyclooxygenase inhibitor, a P2Y1 receptor antagonist, or a K+ATP channel blocking agent. These data suggest that the vasopressor response to ATPgammaS in the mesenteric vascular bed of the cat is mediated via P2X1 receptor activation. The differential responses to ATPgammaS in the hindlimb and mesentery suggest differences in purinergic receptor distribution in the vascular system of the cat. In addition, the results suggest that prostaglandin synthesis, P2Y1 receptor activation, alpha receptor inhibition, and K+ATP channels activation play little to no role in mediating the vascular response to ATPgammaS in the mesentery of the cat.

Adamantane↗
PubMed1984

Meclofenamate treatment of recurrent idiopathic nephrotic syndrome with focal segmental glomerulosclerosis after renal transplantation.

Recurrent corticosteroid-resistant nephrotic syndrome with focal segmental glomerulosclerosis (FSGS) caused the failure of a first renal allograft in a 41-year-old man. Recurrence of the nephrotic syndrome in the second renal allograft was successfully controlled by the administration of meclofenamate, and the renal function has remained stable for 2 1/2 years. No accepted treatment is available for corticosteroid-resistant nephrotic syndrome with FSGS. This report suggests that administration of meclofenamate might be beneficial in some patients with corticosteroid-resistant nephrotic syndrome and FSGS. Because of the potential side effects, however, careful supervision of this therapy is of the utmost importance.

Adult↗
PubMed1985

Treatment of severe nephrotic syndrome with meclofenamate: an uncontrolled pilot study.

The effect of meclofenamate on urinary protein excretion, level of serum albumin, and renal function was studied prospectively in 30 patients with corticosteroid-resistant severe nephrotic syndrome: 16 with focal segmental glomerulosclerosis, 12 with membranous glomerulopathy, and 2 with minimal-lesion nephropathy. Seventeen patients had a 40% or more reduction in urinary protein excretion ("responders"), and the decrease continued during long-term treatment. Meclofenamate therapy was discontinued after 2 months in eight "nonresponders" and in five other patients because of side effects (progressive increase in the level of serum creatinine in two, diarrhea in two, and pruritus in one). In responders, we recorded the following findings (mean +/- SD): urinary protein excretion decreased from 13.0 +/- 5.2 g/24 h to 7.2 +/- 3.5 g/24 h in 2 to 4 weeks and continued to decrease to 4.1 +/- 1.4 g/24 h at the time of the last follow-up study (median duration, 12 months; range, 6 to 36 months; P less than 0.01, 2 to 4 weeks versus later follow-up); the level of serum albumin increased from 1.9 +/- 0.5 g/dl to 2.9 +/- 0.7 g/dl (P less than 0.001) in 2 to 4 weeks; the level of serum cholesterol decreased from 413 +/- 125 mg/dl to 346 +/- 114 mg/dl (P less than 0.005) at the time of the last follow-up examination; and renal function remained unchanged from the baseline study to the follow-up study (serum creatinine 1.5 +/- 0.5 mg/dl versus 1.6 +/- 0.4 mg/dl and glomerular filtration rate 60.5 +/- 29.2 ml/min per 1.7 m2 versus 64.1 +/- 25.5 ml/min per 1.7 m2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1979

Central cardiovascular and thermal effects of prostaglandin F2 alpha in rats.

Administration of PGF2 ALPHA (0.2--6.4 micrograms) into the lateral cerebral ventricle (i.c.v.) induced dose-dependent increases in blood pressure, heart rate and body temperature in urethane-anaesthetised rats, but had no effect on these parameters when the same dose range was administered intravenously. Peripheral pretreatment with sodium meclofenamate (50 mg/kg s.c.) shifted all the dose-response curves for PGF2 alpha (i.c.v.) to the left, but indomethacin (50 mg/kg s.c.) did not significantly affect those changes. Central pretreatment with sodium meclofenamate or indomethacin (1.25 mg per rat i.c.v.) failed to modify significantly the effects of centrally administered PGF2 alpha. The results support previous suggestions that PGF2 alpha may participate in the central control of the cardiovascular and thermoregulatory systems, and also suggest that there may be differences in the sites and/or modes of action between sodium meclofenamate and indomethacin.

Animals↗
PubMed1999

Effects of angiogenic growth factors on endothelium-derived prostacyclin production by ovine uterine and placental arteries.

Uteroplacental and fetoplacental arteries produce substantial amounts of prostacyclin (PGI2). Because angiogenic growth factors such as basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) are increased in pregnancy, we hypothesized that treatment of uterine and fetoplacental arteries with bFGF, VEGF, and EGF would further enhance the pregnancy-induced increase in PGI2 production. Duplicate uterine (UA) and fetoplacental (PA) artery (primary branch off of the umbilical cord = pPA; cotyledonary or tertiary = tPA) explants from seven late gestation sheep were placed in tissue culture (RPMI; 37 degrees C) for 24 h alone or with (1-100 ng/mL) bFGF, VEGF, or EGF. To evaluate the endothelial contribution to basal and stimulated PGI2 production and to determine whether it is de novo, arteries with and without endothelium from three additional late gestation ewes, tissues were incubated in the absence or presence of growth factors with or without meclofenamate (1 microM). The stable metabolite of PGI2, 6-keto-PGF1 alpha, was measured in culture media and expressed as ng/mg wet wt 24 h. PGI2 production by UA increased (p < 0.05) from 5.43 +/- 0.26 at control to 8.93 +/- 0.99 with 100 ng/mL bFGF. Although VEGF produced a similar response, EGF did not increase PGI2 production in UA. In pPA, 100 ng/mL bFGF induced a 2.2-fold increase (p < 0.01) in PGI2 production from 1.94 +/- 0.14 to 4.20 +/- 0.31; VEGF and EGF were without effect. In tPA, 50 and 100 ng/mL bFGF increased PGI2 production from 1.98 +/- 0.14 to 3.5 +/- 1.05 and 3.96 +/- 0.46 (p < 0.02). In tPA, VEGF did not increase PGI2 production; however, 10, 50, and 100 ng/mL EGF, enhanced (p < 0.03) PGI2 production from 1.98 +/- 0.14 to 3.39 +/- 0.62, 3.62 +/- 0.26, and 2.93 +/- 0.20. Endothelium removal and meclofenamate treatment caused a 90% and 100% decrease, respectively, in basal PGI2 production, with no recovery after treatment with growth factors. We conclude that PGI2 production is augmented by bFGF in UA, pPA and tPA, by VEGF in UA, and by EGF in tPA during ovine pregnancy. Basal and stimulated PGI2 secretion is endothelium-derived via de novo synthesis. bFGF, VEGF, and EGF, in addition to angiogenesis, may modulate PGI2 production, further enhancing blood flow to the growing uteroplacental bed.

Animals↗
PubMed1986

Effects of oral meclofenamate therapy in psoriasis.

One hundred three patients entered a study to evaluate the effects of oral meclofenamate sodium therapy on psoriasis. The first 4 weeks of the study were double-blind, with patients receiving either meclofenamate or placebo. Most patients receiving meclofenamate had no change in their psoriasis, in comparison with their pretherapy condition. There was no difference in the response of the psoriasis between the group taking meclofenamate and the group taking placebo. Eighty-nine patients continued in a 4-week open trial of meclofenamate. Approximately one third of the patients showed improvement, but this result appeared to be related to the open trial design. Since oral meclofenamate therapy was not associated with frequent worsening of psoriasis, it is an appropriate treatment for psoriatic arthritis.

Administration, Oral↗