UMLS:C0406810 - FACTA Search

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Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study, we investigated a protective role of constitutively occurred nitric oxide (NO) against indomethacin-induced intestinal lesions in rats. Indomethacin (10 mg/kg) was given s.c. to animals without fasting, and the intestinal mucosa was examined for lesions 24 h later. The NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) was given s.c. 0.5 h before or 6 hr after indomethacin, while the NO donor (+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexnamine (NOR-3) was given s.c. 0.5 h before indomethacin. Indomethacin caused hemorrhagic lesions in the small intestine, accompanied with an increase in intestinal motility and bacterial translocation. These lesions were markedly prevented or worsened, respectively, by later or prior administration of L-NAME (20 mg/kg), in a L-arginine-sensitive manner. The worsening effect of L-NAME (5-20 mg/kg) on these lesions was dose-dependently observed in association with further enhancement of the bacterial translocation and intestinal hypermotility following indomethacin. By contrast, prior administration of NOR-3 (1-6 mg/kg) dose-dependently prevented the development of intestinal lesions, together with suppression of the bacterial translocation and intestinal hypermotility in response to indomethacin. On the other hand, both indomethacin and L-NAME decreased intestinal mucus and fluid (water) secretion in the small intestine, while NOR-3 increased these secretions. These results suggest that (1) NO occurred constitutively exerts a protective action against indomethacin-induced intestinal ulceration, and (2) this effect is related with prevention of bacterial translocation, the process functionally associated with increase of mucus and fluid secretions as well as inhibition of intestinal hypermotility.
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PMID:Protection by constitutively formed nitric oxide of intestinal damage induced by indomethacin in rats. 1159 16

To evaluate the modulating effects of nitric oxide and prostanoids during angiotensin II-mediated vasoconstriction, male Wistar rats (n=25) were infused with increasing doses of angiotensin II following pretreatment with the cyclooxygenase inhibitor indomethacin, the nitric oxide-synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) plus sodium nitroprusside to restore mean arterial blood pressure, or saline. Hemodynamics were studied with the radioactive microsphere method. Indomethacin did not alter systemic or regional hemodynamics. L-NAME+sodium nitroprusside reduced cardiac output, as well as systemic and renal vascular conductance. Angiotensin II increased mean arterial blood pressure and heart rate, and decreased systemic vascular conductance as well as vascular conductance in gastrointestinal tract, kidney, skeletal muscle, skin, mesentery+pancreas, spleen and adrenal. Indomethacin enhanced the angiotensin II-mediated effects in all vascular beds, whereas L-NAME+sodium nitroprusside enhanced its effect in mesentery+pancreas only. In conclusion, vasodilator prostanoids, but not nitric oxide, counterregulate angiotensin II-mediated vasoconstriction in vivo.
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PMID:Prostanoids, but not nitric oxide, counterregulate angiotensin II mediated vasoconstriction in vivo. 1168 91

Specific cerebrovascular dilatory responses in newborn piglets are entirely prostanoid dependent, but require both nitric oxide (NO) and prostanoids in juveniles. We examined endothelial dependency and mechanisms of NO- and prostanoid-mediated cerebrovascular responses in anesthetized newborn and juvenile pigs implanted with closed cranial windows. Light/dye endothelial injury inhibited newborn and juvenile hypercapnic and bradykinin (BK) responses and inhibited dilation to acetylcholine in juveniles. Iloprost and NO act permissively in restoring light/dye inhibited newborn and juvenile responses, respectively. Differences in sensitivity to iloprost and sodium nitroprusside were not observed. Juvenile (not newborn) hypercapnic and BK cerebrovascular responses were sensitive to soluble guanylyl cyclase inhibition. Pial arteriolar diameter and cortical production of prostacyclin, cAMP, and cGMP in response to BK were measured under control conditions, after treatment with indomethacin and/or N(omega)-nitro-L-arginine methyl ester (L-NAME). Indomethacin inhibited BK responses in newborns. Juvenile responses were inhibited by L-NAME, and mildly by indomethacin. Cortical 6-keto-PGF(1 alpha), cAMP, and cGMP increased in response to BK in both age groups. Newborn cerebrovascular responses are largely NO independent, but NO becomes more important with maturation.
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PMID:Endothelial NO and prostanoid involvement in newborn and juvenile pig pial arteriolar vasomotor responses. 1170 1

Changes in vascular responsiveness are the basis for some of the cardiovascular complications in cholestasis. Since the duration of cholestasis is important in determining the degree of the complications, we investigated the time-course dependent evolution of vascular relaxation responsiveness in the aortic rings of cholestatic rats. Acetylcholine-induced endothelium-dependent relaxation was investigated in the isolated aortic rings of unoperated, sham-operated and two-, five-, seven- and fourteen-day bile-duct ligated rats. There was a significant reduction in acetylcholine-induced relaxation of the aortic rings by the second day after the bile-duct ligation operation, compared to those of unoperated and sham-operated groups, but more reduction still occurs in 5- and 7-day bile-duct ligated groups, reaching a plateau by the seventh day. The relaxation response to sodium nitroprusside in the aortic rings of the unoperated and the 7-day bile-duct ligated rats did not differ, implying the intact smooth muscle component of the relaxation pathway. L-NAME ( N(omega)-nitro-L-arginine methyl ester), a nitric oxide (NO) synthase inhibitor, attenuated the acetylcholine-induced relaxation in both groups (unoperated and bile-duct ligated), while L-arginine prevents this inhibitory effect. Indomethacin potentiated the acetylcholine-induced relaxation in the aortic rings of the bile-duct ligated rats while it has no effect on unoperated controls, providing evidence for the possible role of vasoconstrictor prostanoids in cholestasis-induced reduction in acetylcholine-induced relaxation. These results state that the reduced acetylcholine-induced relaxation in the cholestatic aortic rings during the first week, when no portal hypertension was reported to be present, may be due to the decreased acetylcholine-induced NO release from endothelium or increased NO inactivation.
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PMID:Time-dependent reduction of acetylcholine-induced relaxation in aortic rings of cholestatic rats. 1173 60

An arteriograph was used to assess myogenic tone, smooth muscle contractility and the influence of endothelial function on mesenteric resistance artery reactivity in insulin-resistant mice (C57BL/KsJ-db/db) and age- and gender-matched wild-type mice. Increases in transmural pressure induced myogenic tone in arteries from both control and db/db mice. At 12 and 16 weeks of age, greater tone developed in diabetic than in control mice. In control, but not in db/db mice, pretreatment of arteries with L-NAME potentiated myogenic tone. Indomethacin and SQ29548 (PGH2/TXA2 receptor antagonist) had no efffect in control, but inhibited myogenic tone in db/db mice. Endothelium-dependent vasodilation induced by acetylcholine and bradykinin, was depressed in db/db mice and potentiated by SQ29548 and LY333531 (protein kinase C(beta) inhibitor). Messenger RNA expression levels for PKC(beta) were over-expressed 2.5-fold in db/db relative to those in control mice. However, expression levels of mRNA for eNOS, PKC(alpha), and PKC(xi) were similar in the db/db and control mice. Collectively, these results suggest that the greater myogenic tone in resistance arteries from diabetic mice may be attributable, to greater amounts of one or more vasoconstricting prostanoids. Our data indicate that in diabetic mice, basal and agonist-stimulated NO releases are depressed and NO-mediated vasorelaxation in these mice may be countered by an endogenous vasoconstrictive prostanoid. This prostanoid-induced vasoconstriction is mediated by a PKC(beta)-dependent mechanism. Therefore, heightened activation of PKC(beta) and release of a vasoconstrictor prostanoid could play a role in endothelial dysfunction associated with type II diabetes.
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PMID:Influence of type II diabetes on arterial tone and endothelial function in murine mesenteric resistance arteries. 1174 Jan 57

Meconium aspiration syndrome (MAS) is a cause of significant morbidity and mortality in the perinatal period. Despite the clinical relevance of MAS, its pathogenesis is poorly understood. Epithelial cell-derived prostanoids are involved in the regulation of several cellular functions within the lung, including the control of tone and reactivity of airway and vascular smooth muscle. In this study, we evaluated whether exposure to meconium affects the metabolic function of human airway epithelial cells. Monolayers of A549 cells, a transformed human epithelial cell line, were incubated with various concentrations of meconium. Control cells were incubated with serum-free medium in a similar manner. The supernatant fluid was removed at various time points and assayed for thromboxane A(2) (TXA(2)) production. The latter was accomplished by measuring its immediate and stable metabolite thromboxane B(2), using an enzyme-linked immunosorbent assay (ELISA). In selected experiments, the modulatory effects of indomethacin (10(-6) M), dexamethasone (10(-6) M), and L-nitroarginine methyl ester (L-NAME, 10(-6) M) on TXA(2) production were evaluated. Results were expressed in terms of pg/mg protein (mean +/- SE). We found that exposure to meconium produced a significant release of TXA(2) from A549 cells. Indomethacin, dexamethasone, and in part, L-NAME inhibited meconium-induced release of TXA(2). Our findings demonstrate that meconium enhances the production of thromboxanes from A549 cells, suggesting that airway epithelial cells and their metabolic products may play an important role in the pathogenesis of MAS.
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PMID:Enhanced release of thromboxane A(2) after exposure of human airway epithelial cells to meconium. 1180 47

Nitric oxide (NO) has been postulated to play a role in pain as well as in inflammation. In the present studies, the effects of NO synthase (NOS) inhibitors on both pain and inflammation were examined in a rat model of polyarthritis. Female Lewis rats were injected intraperitoneally (i.p.) with peptidoglycan/polysaccharide (PG/PS) or saline to induce arthritis. Hind paw volume, response latency to thermal nociceptive stimulus and mechanical threshold were measured daily for the next 35 days. Paw inflammation, thermal hyperalgesia and mechanical allodynia developed in all rats that received PG/PS compared to saline. On day 19 (chronic inflammation phase), rats were given either N(G)-nitro-L-arginine methyl ester (L-NAME, non-selective NOS inhibitor, 100 mg/l), L-N (6)-(1-iminoethyl) lysine (L-NIL, selective inducible NOS inhibitor, 10 mg/l) or no drug in drinking water. By day 21, L-NAME treatment reversed the thermal hyperalgesia completely and this effect remained until day 35. Similarly, L-NIL treatment reversed thermal hyperalgesia from days 24 to 34. Neither treatment affected mechanical allodynia. Paw volume was not different between PG/PS treated and PG/PS plus L-NAME treated rats. However, the PG/PS plus L-NIL treatment produced an increase in paw volume greater than did PG/PS alone. Other rats were treated with PG/PS plus the antiinflammatory agent indomethacin (days 19-35). Indomethacin treatment reversed all the measured parameters, although the reversal of mechanical allodynia was only partial. These results suggest that NO is involved in thermal, but not mechanical sensory pathways and that the selective inhibition of inducible NOS activity exacerbates established inflammation.
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PMID:Therapeutic administration of nitric oxide synthase inhibitors reverses hyperalgesia but not inflammation in a rat model of polyarthritis. 1183 21

1. The proton pump inhibitors lansoprazole (LP) and omeprazole (OP) and the cholecystokinin (CCK)-receptor antagonist PD-136450 (PD) provide a broad spectrum of activities in their ability to inhibit gastric acid secretion and protect the stomach against ulcerogens. In the present study, we investigated the protective effects of these compounds against gastric ulcers induced by acidified ethanol (AE) and indomethacin. 2. Both AE (60% ethanol in 150 mmol/L HCl, 1 mL/rat) and indomethacin (30 mg/kg) produced gastric haemorrhagic lesions in the rat 1 and 6 h after oral administration, respectively. 3. The gastric mucosal protective effects of LP (1-20 mg/kg), OP (0.5-10 mg/kg) and PD (1-20 mg/kg), administered either orally or subcutaneously (s.c.) 30 min before the administration of AE or indomethacin, were dose dependent against both models of ulcer induction. 4. To determine whether the cytoprotective effect of LP, OP and PD (each 10 mg/kg) was mediated by endogenous prostaglandins (PG), indomethacin (10 mg/kg, s.c.) was administered 15 min before AE to inhibit prostanoids biosynthesis. Indomethacin reduced the cytoprotective effects of OP, but not LP, administered either orally or s.c. Indomethacin reduced the cytoprotective effect of PD administered orally, although the effect was much less significant than when PD was administered s.c. The results exclude the role of PG in mediating the protective effects of LP, whereas the possibility exists for PG to have a role in mediating the protective effects of OP and PD. 5. To investigate the possible involvement of endogenous nitric oxide (NO) in the cytoprotective action of LP, OP and PD, we treated rats with a selective inhibitor of NO synthesis, namely NG-nitro-L-arginine methyl ester (L-NAME; 25 mg/kg, s.c.). Administration of L-NAME 15 min prior to LP, OP or PD (each 10 mg/kg) orally or s.c. and challenge with AE or indomethacin did not significantly increase the degree of the ulcer index and L-NAME was not able to antagonize the protective effects of LP, OP and PD, thus excluding the role of NO in mediating the protective effects of these drugs. However, the effects of PD in reducing the indomethacin-induced ulcer index were less significant in the presence than the absence of L-NAME (P < 0.05 vs P < 0.001, respectively), suggesting a role for NO. 6. In conclusion, the results of the present study suggest that LP and OP are equally effective against AE- as well as indomethacin-induced gastric ulcers and were more potent than PD in protecting the stomach against ulcer formation. Lansoprazole, OP and PD bring about their cytoprotective action through the reduction of acid secretion and some other unknown mechanisms. However, OP and PD may exert their cytoprotective action through PG and NO pathways.
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PMID:A comparative study on the activity of lansoprazole, omeprazole and PD-136450 on acidified ethanol- and indomethacin-induced gastric lesions in the rat. 1190 79

Phoneutria nigriventer spider venom has been described as acting on several cardiovascular sites. In the present paper, a semi-purified fraction of this spider venom was studied to observe any contractile or relaxing effect in rat mesenteric arterial rings (MAR). Spider venom was first fractionated by gel filtration and subsequently by gradual isocratic steps in 0.1% trifluoroacetic acid. The first fraction of this last fractionation step is studied in the present paper and due to its main effect, it was named NORF (nitric oxide releasing fraction). No direct contractile effect was induced by NORF in relaxed MAR, suggesting no NORF-induced neurotransmitter release in this preparation. No significant influence of NORF was observed on concentration-response curves to phenylephrine on endothelium-denuded MAR, but a significant inhibitory shift of concentration-respense curves was observed on endothelium-preserved MAR (EC50 = 0.39 +/- 0.07 microM for control and EC50 = 0.68 +/- 0.14 microM with NORF). NORF induced concentration-dependent relaxation in endothelium-preserved phenylephrine pre-contracted MAR but not in endothelium-denuded MAR. NORF-induced relaxation was inhibited by the nitric oxide synthase inhibitor L-NAME (N(omega)-nitro-arginine methyl ester). Indomethacin or HOE-140 (D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin) had no significant effect on NORF-induced relaxation. Acetylcholine- and NORF-induced relaxation of pre-contracted MAR were differently inhibited by atropine. The pA2 value for atropine-acetylcholine was 9.78 +/- 0.06 and that for atropine-NORF was 8.53 +/- 0.30 (P<0.01). These observations suggest that NORF induces concentration-dependent liberation of nitric oxide from MAR endothelium and that a non-muscarinic mechanism might be involved in this effect. Our data suggest no involvement of prostanoids or bradykinin in the relaxing mechanism.
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PMID:Endothelium-dependent relaxation of rat mesenteric arterial rings by a Phoneutria nigriventer venom fraction. 1192 20

We investigated a possible contribution of nitric oxide (NO) and prostaglandins to the inhibitory effect of losartan on contractions to Ang I (10(-6) M) and Ang II (10(-7) M) with or without L-NAME (10(-4) M) or indomethacin (10(-5) M) in the aorta of WKY, SHR and hamster (n=7 each). Rings of thoracic aorta (2-mm long) were placed in a myograph (5 ml). Endothelium-dependent vasodilations were evaluated with acetylcholine (10(-8) to 10(-6) M). After a 45-minute incubation with L-NAME under a resting tension of 2 g, only hamster aorta contracted (p<0.01). The SHR aorta showed impaired relaxations to acetylcholine compared with the WKY and hamster aorta (p<0.05). Despite the difference in the stimulated NO release, losartan completely abolished the responses to Ang I and Ang II both in WKY and SHR vessels irrespective of the presence of L-NAME. In contrast to the rat aorta, the inhibitory effect of losartan was attenuated in the presence of L-NAME in the hamster aorta (78% vs 99% inhibition, p<0.05). Indomethacin did not alter the effect of losartan in any vessels. Our results suggest that the presence of NO, particularly a basal secretion of NO, is necessary for the full expression of the inhibitory effect of losartan in the hamster, but not in WKY or SHR, aorta. Unlike NO, prostaglandins do not appear to play a role in the effect of losartan.
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PMID:Nitric oxide mediates inhibitory effect of losartan on angiotensin-induced contractions in hamster but not rat aorta. 1196 11

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