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)

Investigations on the effects of insulin on the normal vasculature have produced conflicting results. This study was aimed at establishing the vasomotor actions of insulin on normal cavernous smooth muscle. Insulin produced dose-dependent (10(-10)-10(-5) M) relaxation of the norepinephrine-precontracted strips of cavernosum, and of Bay K8644 [methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-2(trifluoromethylphenyl)pyridine-5-carboxylate]-precontracted strips. Endothelial denudation or indomethacin (10 microM) pre-treatment significantly reduced these insulin-induced relaxations, whereas NG-nitro-L-arginine methyl ester (L-NAME, 5 mM) did not. Moreover, the pre-treatment of the cavernosum strips with a prostacyclin synthesis inhibitor [9,11-diazo-15-deoxy-prostaglandin H2 (U-51605), 10 microM] significantly reduced insulin-induced response, whereas pretreatment with a cyclooxygenase-2 (COX-2) inhibitor (NS-398, 10 microM) did not. In addition, responses to insulin were not inhibited by K+ channel blockers, i.e., tetraethylammonium (TEA, 10 mM) or 4-aminopyridine (4-AP, 10 microM). Moreover, L-type Ca2+ currents were reduced by prostacyclin (2 microM) but not by insulin (10 microM). We conclude that insulin induces the endothelium-dependent relaxation of cavernous smooth muscles and that this relaxation response may emanate from the direct inhibition of L-type Ca2+ channels by prostacyclin.
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PMID:Vasomotor action of insulin on the rabbit normal cavernous smooth muscle. 1659 39

Nitric oxide synthases (NOS) and cyclooxygenase-2 (COX-2) are important enzymes involved in ulcer healing but interactions between them have not been clearly defined. The aim of this study was to investigate the effects of selective or non-selective inhibition of NOS on the expression and activity of COX-2 during healing of acetic acid-induced gastric ulcers in rats. N-[3-(aminomethyl)benzyl] acetamidine (1400 W), a potent selective inhibitor of inducible nitric oxide synthase (iNOS), at a dose of 0.1 mg/kg/day, was found to reduce the ulcer sizes at day 3 and 7 post-ulcer induction. On the other hand, 15 mg/kg/day of NG-nitro-L-arginine methyl ester (L-NAME), a non-selective NOS inhibitor that suppresses both iNOS and endothelial nitric oxide synthase (eNOS), enlarged the ulcer sizes over the same time periods. The expression of COX-2 and COX activity, together with NF-kappaB activation in the ulcer tissues were down-regulated by L-NAME but not 1400 W. It is concluded that iNOS may contribute to ulcer formation while COX-2 and eNOS promote ulcer healing. eNOS enhances COX-2 expression possibly through the activation of NF-kappaB.
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PMID:Differential effects of selective and non-selective inhibition of nitric oxide synthase on the expression and activity of cyclooxygenase-2 during gastric ulcer healing. 1660 Feb 10

A novel 14-kDa lectin from Annona coriacea seeds (ACLEC) with hemagglutinating activity on erythrocytes has been recently described. Since plant lectins are known to present inflammatory activity, this study aimed to investigate the leukocyte migration induced by ACLEC, and inflammatory mediators involved in this phenomenon. Male Swiss mice were intraperitoneally injected with ACLEC (3-100 microg/cavity), and at 4-96 h thereafter the leukocyte counts in peritoneal lavage fluid were evaluated. ACLEC induced a dose-dependent neutrophil accumulation, reaching maximal responses at 16 h after injection (approximately 40-fold increase for 30 microg/cavity). Significant accumulation of mononuclear cells was observed at 72 h (2.7-fold increase). The carbohydrate mannose nearly abolished the neutrophil influx, whereas sucrose, glucose and galactose had no effect. Dexamethasone, the cyclooxygenase-2 (COX-2) inhibitor celecoxib and the Platelet activating factor (PAF) receptor antagonist PCA4248 significantly reduced ACLEC-induced neutrophil influx. The tachykinin NK(1) antagonist SR140333, the tachykinin NK(2) antagonist SR48968, the non-selective NO inhibitor L-NAME, the selective inducible NOS inhibitor aminoguanidine and the lypoxygenase inhibitor AA861 all failed to modify the ACLEC-induced responses. In conclusion, ACLEC is able to attract neutrophils into the mice peritoneal cavity by mechanisms involving interactions of the lectin with cell-specific mannose recognition, leading to the release of COX-2-derived mediators and PAF.
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PMID:Neutrophil migration in mice induced by a mannose-binding lectin isolated from Annona coriacea seeds. 1692 40

The in vitro exposure to anandamide elicits greater relaxations in mesenteric beds isolated from female compared to male rats. The present work shows that in mesenteric beds precontracted with noradrenaline the removal of endothelium increased the relaxation caused by anandamide in male and ovariectomized female but not in sham-operated female rats. The nitric oxide synthase inhibition with 100 microM N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME) and the sensory in vivo denervation through neonatal administration of capsaicin also reduced anandamide-induced relaxations but these effects had the same extent in male and in female mesenteries. The content of calcitonin gene related peptide (CGRP) in mesenteric beds, that was higher in intact female than in male rats, was reduced by ovariectomy and restored to control values 21 days after a 3 weekly i.m. administration of 450 microg/kg 17beta-oestradiol. This latter treatment also increased CGRP content in mesenteries from males up to the same levels observed in females. The basal release of CGRP in mesenteric beds was equivalent in either sex, but the exposure to anandamide increased CGRP release solely in female mesenteries. The ratio prostacyclin/thromboxane A(2) was selectively reduced in mesenteries from male rats after exposure to anandamide, due to the decrease of the tissue levels of prostacyclin. Moreover, the cyclooxygenase-2 inhibitor 0.1 microM N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulphonamide (NS-398) diminished the relaxations caused by anandamide solely in female rats. It is proposed that relaxing factors such as CGRP and prostacyclin contribute to the higher relaxations caused by anandamide in the vasculature of female rats.
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PMID:Participation of CGRP and prostanoids in the sex-linked differences of vascular anandamide effects in mesenteric beds of Sprague-Dawley rats. 1716 58

LCY-2-CHO has anti-inflammatory actions on macrophages. To understand its therapeutic implication in atherosclerosis, we examined its effects on the expressions of anti-inflammatory and inflammatory proteins in cultured rat aortic vascular smooth muscle cells (VSMC). LCY-2-CHO is able to induce heme oxygenase-1 (HO-1) protein expression through a transcriptional action. The HO-1 inducting effect of LCY-2-CHO was inhibited by SB203580, N(G)-nitro-l-arginine methylester (l-NAME), and wortmannin, but was not affected by U0126 or SP600125. In accordance LCY-2-CHO increased protein phosphorylation of p38, Akt, and eNOS. Nrf2 is a transcription factor essential for HO-1 gene induction and we showed that LCY-2-CHO is able to cause Nrf2 nuclear translocation and this action depends on p38, Akt and eNOS. In addition to induce anti-inflammatory HO-1, LCY-2-CHO reduced interleukin-1beta (IL-1beta)-induced inflammatory mediators, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), growth-related oncogene protein-alpha (GRO-alpha), and interleukin-8 (IL-8). Inhibitory effect on IL-1beta-mediated NF-kappaB activation was evidenced by the diminishment of IkappaB kinase (IKK) phosphorylation and IkappaBalpha degradation. In contrast, IL-1beta-mediated ERK and JNK activations were not changed by LCY-2-CHO, while p38 activation by IL-1beta and LCY-2-CHO displayed the non-additivity. Taken together, given the overall anti-inflammatory properties of LCY-2-CHO in VSMC, in terms to induce HO-1 gene expression and inhibit inflammatory gene expression, these results highlight the therapeutic potential of LCY-2-CHO in atherosclerosis.
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PMID:The anti-inflammatory actions of LCY-2-CHO, a carbazole analogue, in vascular smooth muscle cells. 1749 20

In this study, the cardioprotective effects of nitric oxide (NO)-aspirin, the nitroderivative of aspirin, were compared with those of aspirin in an anesthetized rat model of myocardial ischemia-reperfusion. Rats were given aspirin or NO-aspirin orally for 7 consecutive days preceding 25 min of myocardial ischemia followed by 48 h of reperfusion (MI/R). Treatment groups included vehicle (Tween 80), aspirin (30 mg.kg(-1).day(-1)), and NO-aspirin (56 mg.kg(-1).day(-1)). NO-aspirin, compared with aspirin, displayed remarkable cardioprotection in rats subjected to MI/R as determined by the mortality rate and infarct size. Mortality rates for vehicle (n = 23), aspirin (n = 22), and NO-aspirin groups (n = 22) were 34.8, 27.3, and 18.2%, respectively. Infarct size of the vehicle group was 44.5 +/- 2.7% of the left ventricle (LV). In contrast, infarct size of the LV decreased in the aspirin- and NO-aspirin-pretreated groups, 36.7 +/- 1.8 and 22.9 +/- 4.3%, respectively (both P < 0.05 compared with vehicle group; P < 0.05, NO-aspirin vs. aspirin ). Moreover, NO-aspirin also improved ischemia-reperfusion-induced myocardial contractile dysfunction on postischemic LV developed pressure. In addition, NO-aspirin downregulated inducible NO synthase (iNOS; 0.37-fold, P < 0.01) and cyclooxygenase-2 (COX-2; 0.61-fold, P < 0.05) gene expression compared with the vehicle group after 48 h of reperfusion. Treatment with N(G)-nitro-L-arginine methyl ester (L-NAME; 20 mg/kg), a nonselective NOS inhibitor, aggravated myocardial damage in terms of mortality and infarct size but attenuated effects when coadministered with NO-aspirin. L-NAME administration did not alter the increase in iNOS and COX-2 expression but did reverse the NO-aspirin-induced inhibition of expression of the two genes. The beneficial effects of NO-aspirin appeared to be derived largely from the NO moiety, which attenuated myocardial injury to limit infarct size and better recovery of LV function following ischemia and reperfusion.
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PMID:Cardioprotective effects of nitric oxide-aspirin in myocardial ischemia-reperfused rats. 1752 56

Polygonum cuspidatum water extract (PCWE) was shown to be a potent inhibitor of lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). PCWE was compared to baicalin isolated from Scutellaria baicalensis Georgi and berberine of Coptidis rhizoma and Phellodendri cortex, for their effects on LPS-induced nitric oxide (NO) production and iNOS and COX-2 gene expressions in RAW 264.7 macrophages. Both PCWE and the compounds inhibited LPS-induced NO production in a concentration-dependent manner without a cytotoxicity. The decrease in NO production was in parallel with the inhibition of LPS-induced iNOS gene expression by PCWE and the compounds. In contrast, iNOS enzyme activity was not inhibited by PCWE and two agents. In addition, only PCWE inhibited LPS-induced prostaglandin E2 (PGE2) production and COX-2 gene expression without affecting COX-2 enzyme activity, while baicalin or berberine did not. Furthermore, N-nitro-L-arginine (NLA) and N-nitro-L-arginine methyl ester (L-NAME) pretreatment enhanced LPS-induced iNOS protein expression, which was inhibited by these PCWE and two agents, although LPS-induced COX-2 protein expression was not affected by NLA and L-NAME. PCWE inhibited PGE2 production and COX-2 protein expression in NLA/LPS or L-NAME/LPS-co-treated RAW 264.7 cell, however, baicalin or berberine did not. From the results, it was concluded that co-treatment with NOS inhibitors and PCWE effectively blocks acute production of NO and inhibits expression of iNOS and COX-2 genes.
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PMID:Polygonum cuspidatum, compared with baicalin and berberine, inhibits inducible nitric oxide synthase and cyclooxygenase-2 gene expressions in RAW 264.7 macrophages. 1755 52

Cyclovirobuxine D is an active compound extracted from Buxus microphylla, which has been used for treating acute myocardial ischemia in China. The present study was to investigate its mechanism on myocardial ischemia. Cyclovirobuxine D significantly increased cardiomyocytes viability injured by oxidation or hypoxia. It significantly reduced the infarct size induced by ligating the coronary artery in rats, and the effect was almost abolished by glibenclamide, a blocker of ATP sensitive potassium channel, but it was not influenced by cyclooxygenase-2 inhibitor celecoxib or estrogen receptor antagonist tamoxifen. In addition, cyclovirobuxine D significantly protected rat aorta endothelial cells against hypoxia and enhanced nitric oxide (NO) release from endothelial cells, which was inhibited by nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine methyl ester (L-NAME). Furthermore, cyclovirobuxine D significantly decreased the weight of venous thrombus in rats. In conclusion, the action mechanism of cyclovirobuxine D on myocardial ischemia may be related with its cytoprotection, K(ATP) channel opening, NO generation stimulating and venous thrombosis inhibiting.
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PMID:Cyclovirobuxine D ameliorates acute myocardial ischemia by K(ATP) channel opening, nitric oxide release and anti-thrombosis. 1755 43

N(G)-Nitro-L-arginine-methyl ester (L-NAME)-induced hypertension is a well established model of experimental hypertension. Although regression experiments are effective at approximating a clinical setting the reversal of already established L-NAME hypertension has not been intensively researched. We investigated whether spontaneous regression of L-NAME hypertension after discontinuing the drug administration was associated with recovery of endothelial dysfunction. Special attention was devoted to NO signaling and endothelium-derived constricting factor (EDCF) formation in various parts of the vascular tree. Male adult Wistar rats were divided into 4 groups: an L-NAME (5 weeks), a spontaneous recovery (5 weeks L-NAME + 3 weeks of recovery) and two age-matched control groups (a 5- and 8-week control group). The NO-mediated and EDCF-mediated components of acetylcholine-induced responses were evaluated in preconstricted small mesenteric and femoral arteries. The activity, mRNA and protein expression of NO synthase together with the mRNA expression of cyclooxygenase were determined in the aorta. L-NAME administration caused hypertension, impaired NO signaling (as indicated by the reduced NO component of acetylcholine-induced relaxation and decreased NO synthase activity) in all arteries investigated and reduced the inner diameter of the femoral artery. Moreover, we observed enhanced cyclooxygenase-dependent EDCF formation in the femoral arteries and enhanced cyclooxygenase-2 expression in the aortas of L-NAME-treated rats. During spontaneous recovery a functional restoration of NO signaling took place in all parts of the vascular tree. However, the increases in systolic blood pressure, EDCF formation, and cyclooxygenase expression and the reduction in femoral artery diameter were not completely restored. We conclude that impaired NO signaling was improved after the cessation of L-NAME administration. However, persisting arterial structural alterations and enhanced EDCF formation may decelerate blood pressure reduction even after the restoration of NO synthase activity.
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PMID:Regression of L-NAME-induced hypertension: the role of nitric oxide and endothelium-derived constricting factor. 1863 92

This study investigates the participation of the endothelial factors in the alpha-adrenoceptor contractile responses in mesenteric resistance arteries from 15 days ouabain-treated (25 microg/kg/day) and untreated rats. Ouabain treatment increased blood pressure and heart rate without changing the contractile response to phenylephrine (3 nM-30 microM). Endothelium removal or N(G)-nitro-L-arginine methyl ester (L-NAME, 100 microM), increased the responses to phenylephrine. The endothelial modulation was similar in both rat groups, but the L-NAME effects were bigger in arteries from ouabain-treated rats. However, the endothelial NOS expression and the relaxation to acetylcholine (0.1 nM-10 microM) remained unaltered after ouabain treatment. The coincubation with L-NAME and indomethacin (100 microM) leftward shifted the concentration-response curves to phenylephrine in arteries from untreated rats similarly to the displacement after incubation only with L-NAME. However, in mesenteric arteries from treated rats, the co-incubation with indomethacin and L-NAME did not alter the response to phenylephrine. The addition of the inhibitor of calcium activated potassium channels tetraethylammonium (2 mM) further leftward shifted the phenylephrine curves only in arteries from untreated rats. Cyclooxygenase-2 (COX-2) expression was greater in vessels from ouabain-treated rats. In conclusion, the chronic ouabain treatment for 15 days modified the participation of endothelial factors in response to phenylephrine in mesenteric resistance arteries, by increasing the release of NO and prostanoids and impairment the endothelium-derived hyperpolarizing factor (EDHF) release. This was accompanied by an increased COX-2 expression. Although this balance avoids changes in the phenylephrine concentration-response curves, these vascular changes might contribute to maintain the ouabain-induced hypertension.
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PMID:Ouabain treatment changes the role of endothelial factors in rat resistance arteries. 1897 49

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