Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Arachidonic acid (0.01-1 microM) induced relaxation of precontracted rings of rabbit saphenous vein, which was counteracted by contraction at concentrations higher than 1 microM. Concentrations higher than 1 microM were required to induce dose-dependent contraction of vena cava and thoracic aorta from the same animals. 2. Pretreatment with a TP receptor antagonist (GR32191B or SQ29548, 3 microM) potentiated the relaxant effect in the saphenous vein, revealed a vasorelaxant component in the vena cava response and did not affect the response of the aorta. 3. Removal of the endothelium from the venous rings, caused a 10 fold rightward shift in the concentration-relaxation curves to arachidonic acid. Whether or not the endothelium was present, the arachidonic acid-induced relaxations were prevented by indomethacin (10 microM) pretreatment. 4. In the saphenous vein, PGE2 was respectively a 50 and 100 fold more potent relaxant prostaglandin than PGI2 and PGD2. Pretreatment with the EP4 receptor antagonist, AH23848B, shifted the concentration-relaxation curves of this tissue to arachidonic acid in a dose-dependent manner. 5. In the presence of 1 microM arachidonic acid, venous rings produced 8-10 fold more PGE2 than did aorta whereas 6keto-PGF1alpha and TXB2 productions remained comparable. 6. Intact rings of saphenous vein relaxed in response to A23187. Pretreatment with L-NAME (100 microM) or indomethacin (10 microM) reduced this response by 50% whereas concomitant pretreatment totally suppressed it. After endothelium removal, the remaining relaxing response to A23187 was prevented by indomethacin but not affected by L-NAME. 7. We conclude that stimulation of the cyclo-oxygenase pathway by arachidonic acid induced endothelium-dependent, PGE2/EP4 mediated relaxation of the rabbit saphenous vein. This process might participate in the A23187-induced relaxation of the saphenous vein and account for a relaxing component in the response of the vena cava to arachidonic acid. It was not observed in thoracic aorta because of the lack of a vasodilatory receptor and/or the poorer ability of this tissue than veins to produce PGE2.
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PMID:The cyclo-oxygenase-dependent regulation of rabbit vein contraction: evidence for a prostaglandin E2-mediated relaxation. 1005 Nov 18

In the present study we have examined the effect of centrally administered non-steroidal anti-inflammatory drugs (NSAIDS), nitric oxide synthase (NOS) inhibitor and melatonin on lipopolysaccharide (LPS)-induced hyperthermia and its anti-dipsogenic effect. Intracerebroventricular (i.c.v.) administration of LPS (100-200 ng/rat) induces a dose dependent elevation in body temperature and decreases water consumption in 24 h water deprived rats. Coadministration of NSAIDS (indomethacin and nimesulide: 10 nM/rat each) with LPS (100 ng) reversed, whereas NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME: 10-20 microg/rat) enhanced LPS-induced hyperthermia. In contrast L-NAME reversed the LPS-induced anti-dipsogenic effect in a dose dependent manner, whereas NSAIDS showed no change in the effect of LPS. Further, centrally administered prostaglandin E2 (PGE2, 0.5-1 microg/rat) produced hyperthermia without affecting the drinking behavior, suggesting that two independent mechanisms operate in LPS-induced hyperthermia and in the anti-dipsogenic effect. The pineal hormone melatonin is known to inhibit cellular damage caused by LPS, produced dose dependent (5-10 nM i.c.v.) inhibition of LPS-induced hyperthermia and adipsia, but failed to reverse the PGE2-induced hyperthermia, shows reversal of LPS-induced hyperthermia by melatonin is due to inhibition of prostaglandin synthesis rather than antagonism of prostaglandin action. The overall study reveals that inhibition of both NO and prostaglandin production by melatonin might be responsible for its reversal of LPS-induced hyperthermia and adipsia.
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PMID:Role of centrally administered melatonin and inhibitors of COX and NOS in LPS-induced hyperthermia and adipsia. 1039 6

Prostaglandin E is a major dilator of the fetal ductus arteriosus (DA), but the role of nitric oxide in fetal ductal dilation has not been established. We studied the effects of a potent nitric oxide synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME), on the fetal DA in rats. L-NAME was injected into the dorsum of pregnant rats, and fetal DA was studied 4 h later with a rapid whole body freezing method. The inner diameters of the DA and the main pulmonary artery were measured on a freezing microtome. The inner diameter ratio of DA to main pulmonary artery (DA/PA) was 1.02+/-0.03 (mean +/- SEM; number of fetuses [n], 21) in normal near-term fetuses. The effect of prostaglandin synthesis inhibition was studied after orogastric administration of indomethacin to pregnant rats. In near-term rats on the 21st day of gestation (term, 21.5 d), a large dose of L-NAME (100 mg/kg) caused only mild ductal constriction, with DA/PA reduced to 0.83+/-0.05 (n = 20). Indomethacin (1 mg/kg) caused moderate ductal constriction, and DA/PA was decreased to 0.65+/-0.05 (n = 21). Combined administration of L-NAME (10 mg/kg) and indomethacin (1 mg/kg) caused severe ductal constriction, with DA/PA of 0.26+/-0.03 (n = 16). In preterm rats on the 19th day of gestation, a moderate dose of L-NAME (10 mg/kg) caused severe ductal constriction, with a DA/PA of 0.32+/-0.05 (n = 24). Indomethacin (1 mg/kg) alone caused only mild ductal constriction, with DA/PA 0.86+/-0.02 (n = 16). In conclusion, prostaglandin has a major role and nitric oxide has a minor role in dilating the DA in the near-term fetal rat. In contrast, nitric oxide has a major role and prostaglandin has a minor role in dilating the DA in preterm fetal rats.
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PMID:The role of nitric oxide in dilating the fetal ductus arteriosus in rats. 1047 46

We examined the roles of endogenous prostaglandins (PGs) and nitric oxide (NO) in the gastroduodenal ulcerogenic responses to hypothermic stress (28 approximately 30 degrees C) in anesthetized rats. Lowering body temperature provoked damage in the gastroduodenal mucosa, with an increase of gastric acid secretion and motility. These responses were completely abolished by bilateral vagotomy or atropine, while 16,16-dimethyl PGE2 decreased the mucosal ulcerogenic response with no effect on acid secretion. The non-selective COX inhibitors, indomethacin or aspirin, worsened these lesions with enhancement of gastric motility and no effect on acid secretion, while the selective COX-2 inhibitor NS-398 did not affect any of these responses. On the other hand, the non-selective NOS inhibitor L-NAME but not aminoguanidine (a relatively selective inhibitor of iNOS), significantly potentiated the acid secretory and mucosal ulcerogenic responses in the stomach but reduced the duodenal damage in response to hypothermia, the effects being antagonized by co-administration of L-arginine. Hypothermia itself decreased duodenal HCO3- secretion under both basal and mucosal acidification-stimulated conditions. Both indomethacin and aspirin further decreased the HCO3- response to the mucosal acidification, while L-NAME significantly increased the HCO3- secretion even under hypothermic conditions, similar to 16,16-dimethyl PGE2. These results suggest that 1) hypothermic stress caused an increase of acid secretion and motility as well as a decrease of duodenal HCO3-secretion, resulting in damage in both the stomach and duodenum, 2) the COX-1 but not COX-2 inhibition worsened these lesions by enhancing gastric motility and further decreasing duodenal HCO3- response, 3) the cNOS but not iNOS inhibition worsened gastric lesions by increasing acid secretion but decreased duodenal damage by increasing HCO3- secretion. Thus, it is assumed that the gastroduodenal ulcerogenic and functional responses to hypothermic stress are modified by cNOS/NO as well as COX-1/PGs.
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PMID:Roles of endogenous prostaglandins and nitric oxide in gastroduodenal ulcerogenic responses induced in rats by hypothermic stress. 1067 20

The effects of noradrenaline (NA) and nitric oxide (NO) on prostaglandins (PGs) and progesterone (P4) secretion during the development of the bovine corpus luteum (CL) were investigated. Bovine luteal cells of early and mid-cycle CL were cultured for 20 to 24 h in medium containing 10% calf serum, washed, and treated with NA or nitrergic agents for an additional 16 h in a serum-free medium. NA (10(-5) M) stimulated P4 from early and mid-cycle CL by 238% and 154% (P < 0.01), respectively. Moreover, although NA induced a twofold increase in PGE2 secretion (P < 0.01) in both examined periods, the effect of NA on PGF2alpha secretion was approximately 1.5 times higher (P < 0.05) in early than in mid-cycle CL. Two NO synthase inhibitors, L-NAME and L-NOARG (both 10(-4) M), stimulated P4 secretion only in mid-luteal cells (P < 0.01), although they did not affect the cells from early CL. Although a NO donor, S-NAP (10(-4) M) inhibited P4 secretion from mid-cycle luteal cells (P < 0.05), it strongly stimulated PGE2 in both examined phases (P < 0.001). On the other hand, the output of PGF2alpha was stimulated by S-NAP only in the cells of the mid-cycle CL (P < 0.01). The overall results suggest that adrenergic and nitrergic agents play opposite roles in the regulation of bovine CL functions. Whereas NA may play a supporting role in luteal development, NO may participate in the functional regression of the bovine CL by inhibiting steroidogenesis.
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PMID:Different actions of noradrenaline and nitric oxide on the output of prostaglandins and progesterone in cultured bovine luteal cells. 1068 Jul 74

The aim of the present study was to investigate the interrelationship of the kinin system, nitric oxide and eicosanoids in the acute phase of antigen-induced arthritis (AIA) in rabbits. The arthritis was induced in immunized rabbits and the following parameters were evaluated 24 hours later: leukocyte influx (total and differential white cell count), vascular permeability (Evans's blue method), and synovial PMN cell infiltrate. PGE2 and LTB4 (radioimmunoassay) levels were quantified in the synovial fluid. The animals were pre-treated with 20mg/kg/day during 14 days with L-NAME or D-NAME and/or Enalapril (0.12 mg/kg/day-14 days), and/or the B2 antagonist of Bradykinin HOE 140 (0.9 mg/kg). Our results showed that L-NAME was effective in the prevention of AIA with reduction of all Inflammatory parameters analyzed. Enalapril partially reverted the L-NAME anti-inflammatory effects. The simultaneous treatment with HOE 140 abolished this reversion and returned the inflammatory parameters to the levels observed in L-NAME treated animals. Our results suggest that pressoric alterations induced by L-NAME could not account for all its anti-inflammatory action in this model of experimental arthritis. Additionally the contribution of the kinin system in AIA was characterized as well as its interaction with eicosanoids and nitric oxide.
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PMID:Interrelationship of the kinin system, nitric oxide and eicosanoids in the antigen-induced arthritis in rabbits. 1070 79

The present article overviews the regulatory mechanism of acid secretion in the stomach after damage with taurocholate (TC), one of the bile acids. Mucosal exposure of a rat stomach to 20 mmol/L TC for 30 min caused a decrease of acid secretion with a concomitant increase in nitric oxide (NO) and prostaglandin (PG) E2 (PGE2) as well as Ca2+ in the luminal contents. Prior administration of N(G)-nitro-L-arginine methyl ester (L-NAME), as well as indomethacin, significantly attenuated the reduction of acid secretion by TC and acid secretion was even increased in the presence of L-NAME. The acid stimulatory effect of L-NAME in the damaged stomach was not mimicked by aminoguanidine and was antagonized by co-administration of L-arginine but not D-arginine. Increased NO release in the damaged stomach was suppressed by pretreatment with L-NAME or co-application of EGTA and the latter also inhibited the increase in luminal Ca2+. The enhanced acid secretory response in the presence of L-NAME was also inhibited by cimetidine, FPL-52694 (a mast cell stabilizer) or sensory deafferentation. Mucosal exposure to TC caused an increase in luminal histamine output, together with a decrease in the number of mucosal mast cells in the stomach. These changes were prevented by FPL-52694 and sensory deafferentation and were also partly suppressed by indomethacin. In addition, the acid stimulatory action of L-NAME in the damaged stomach was significantly mitigated when indomethacin was administered together with L-NAME. We conclude that: (i) damage in the stomach may activate acid a stimulatory pathway in addition to a PG-, NO- and Ca2+-dependent inhibitory mechanism, but the latter effect overcomes the former, resulting in a decrease in acid secretion; (ii) acid stimulation in the damaged stomach is mediated by histamine released from the mucosal mast cell, a process interacting with capsaicin-sensitive sensory nerves; (iii) the increase in luminal Ca2+ plays a role in increasing NO production and, hence, in regulating acid secretion; and (iv) PG may have a dual role in the regulation of acid secretion in the damaged stomach: an inhibitory effect at the parietal cell and an excitatory effect, probably through enhancing the release of mucosal histamine.
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PMID:Regulatory mechanism of acid secretion in the damaged stomach: role of endogenous nitric oxide. 1075 19

The present study was designed to investigate the role of nitric oxide (NO), N-methyl-D-aspartate (NMDA) receptor and prostaglandins on hyperalgesia induced in rats by excitatory amino acids and the possibility that prostaglandins may act as the retrograde messenger in the spinal cord like NO. Nomega-nitro-L-arginine methyl ester (L-NAME; 500 microg/paw, intraplantarly (i.pl.)), MK-801 (10 microg/paw, i.pl.) or indomethacin (300 microg/paw, i.pl.) reduced the duration of phase 2 of the biting/licking and scratching (B/L + S) response induced by formalin injection from 255.6+/-16.7 s to 155.6+/-16.9, 172.25+/-33.3 or 205.6+/-16.7 s, respectively. L-NAME (0.3 mg, i.th.), MK-801 (8 microg, i.th.) or indomethacin (20 microg, i.th) reduced the duration of phase 2 of the B/L + S response induced by saline injection from 288.5+/-7.7s to 207.7+/-19.2, 184.6+/-7.7 or 1923+/-38.5 s, respectively. L-NAME or indomethacin injected into the spinal cord of the rat significantly reduced the hyperalgesia induced by NMDA (1 microg, i.th.) from 43.8+/-4.6% to 12.3+/-3.1 and 19.2+/-2.3%, respectively. It is assumed that NO produced by excitatory amino acids may increase prostaglandin production by cyclooxygenase activation. L-NAME, MK-801 or indomethacin injected into the rat spinal cord significantly reduced the hyperalgesia induced by prostaglandin E2 (PGE2, 25 ng, i.th.) in the tail-flick test from 40.6+/-3.5% to 18.2+/-3.2, 18.8+/-1.8 or 17.6+/-4.1%, respectively, but had little effect on hyperalgesia in the paw pressure test (except for indomethacin). In conclusion, NO and PGE2 affect the hyperalgesia induced by excitatory amino acids. It is suggested that PGE2, like NO, may act as a retrograde messenger in the spinal cord.
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PMID:The role of nitric oxide and prostaglandin E2 on the hyperalgesia induced by excitatory amino acids in rats. 1081 54

We have studied the effect of nitric oxide (NO) on the production of arachidonic acid ([14C]-AA) metabolites in the rat oviduct. The basal synthesis of eicosanoids was measured by the conversion of ([14C]-AA) to the different radiolabeled products of cyclooxygenase (COX). The oviducts incubated for 1 h with the labeled substrate of COX were able to convert 3.3 +/- 0.3% of ([14C]-AA) to 6-ceto-PGF1alpha, 10.7 +/- 1.0% to PGF2alpha, 13.5 +/- 1.2% to PGE2 and 6.3 +/- 0.5% to TXB2. The tissues were incubated with different doses of two NO donors: SIN-1 and Spermine NONOate. The results indicated that SIN-1 produces a significant decrease (50%; P < 0.05) in all prostanoids evaluated in a dose-response fashion. The inhibitory effect was completely reversed by addition of 20 microg/ml of hemoglobin (Hb), a NO scavenger. The addition of Spermine NONOate to the incubation medium diminished significantly (65%) the synthesis of COX metabolites suggesting that NO acts by inhibiting COX activity in the rat oviduct. However, NOS inhibitors, N(G)-L-arginine-methyl-ester (L-NAME) nd N(G)-L-monomethyl-arginine (L-NMMA) had no effect on basal production of the prostanoids. These results indicate that in the rat oviduct the synthesis of COX metabolites is negatively regulated by nitric oxide.
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PMID:Nitric oxide inhibits prostanoid synthesis in the rat oviduct. 1088 88

Duodenal HCO3- secretion increases in response to mucosal acidification by luminal acid. Although this process is known to be mediated by endogenous prostaglandins (PGs), the role of nitric oxide (NO) in this response has been little studied. We examined the effects of indomethacin and N(G)-nitro-L-arginine methyl ester (L-NAME) on the acid-induced HCO3- secretion in the rat duodenum, together with those on PGE2 generation as well as luminal release of NO metabolites (NOx). A proximal duodenal loop was perfused with saline, and the HCO3- secretion was measured at pH 7.0 using a pH-stat method and by adding 10 mM HCl. Mucosal acidification was performed by exposing the loop to 10 or 100 mM HCl for 10 min. Acidification of the duodenal mucosa stimulated the HCO3- secretion, with concomitant increase of mucosal PGE2 contents and luminal release of NOx, the response being much greater in case of 100 mM HCl. Indomethacin significantly inhibited the acid-induced HCO3- secretion as well as the PGE2 biosynthetic response, without influence on the NOx release. Pretreatment of the animals with L-NAME attenuated both the increase of mucosal PGE2 contents and luminal release of NOx following the acidification, resulting in a marked inhibition of the acid-induced HCO3- response, and these effects were significantly antagonized by coadministration of L-arginine. Duodenal HCO3- secretion was also increased by mucosal exposure to NOR-3 (a NO donor), with concomitant increase of PGE2 generation, but these effects were mitigated in the presence of indomethacin. In addition, the duodenal damage caused by mucosal perfusion with 100 mM HCl for 4 hr was markedly aggravated by pretreatment with L-NAME as well as indomethacin. These results suggest that both endogenous NO and PGs are involved in the mechanism for the acid-induced duodenal HCO3- secretion, and that NO may increase the HCO3- secretion by stimulating PG generation.
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PMID:Role of endogenous nitric oxide and prostaglandin in duodenal bicarbonate response induced by mucosal acidification in rats. 1141 96


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