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)

To characterize alterations of renal vessels occurring during systemic hypertension elicited in rats by 5, 10, and 25 days of treatment by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME)(20 mg/kg daily), preglomerular vasculatures, consisting of arcuate arteries and their branches, interlobular arteries, and afferent arterioles, were isolated by HCl maceration. Blockade of nitric oxide synthase significantly increased tail-cuff systolic blood pressure by 21 +/- 2% and 42 +/- 3% after 5 and 25 days, respectively. Medias of hypertensive arcuate arterial branches and interlobular arteries but not of afferent arterioles had focal deposits of Sudan black-positive lipid droplets. At 25 days, vessel wall thickness increased by 72 +/- 6% along the sudanophilic areas. Immunostaining of sudanophilic lesions with a panel of antibodies unveiled medial cell proliferation, macrophage invasion, immunoreactive vascular cell adhesion molecule-1, and low-density lipoprotein. The frequency of sudanophilic lesions increased with time to affect 26 +/- 2% and 36 +/- 3% of arcuate arterial branches and interlobular arteries, respectively, at 25 days. Hypertensive L-NAME-treated rats developed glomerular injury probed by albuminuria and glomerular immunostaining for alpha-smooth muscle actin. Administration of the nonselective endothelin antagonist bosentan (30 mg/kg daily) blunted the development of sudanophilic lesions during L-NAME treatment without affecting arterial hypertension or degree of glomerular injury. Therefore, L-NAME hypertension leads to rapid development of focal, inflammatory, proliferative, and sudanophilic lesions along preglomerular vessels, suggesting atherosclerosis-like processes. Furthermore, endothelin is a likely mediator in the development of these lesions.
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PMID:Preglomerular sudanophilia in L-NAME hypertensive rats: involvement of endothelin. 869 42

Chronic blockade of NO production induces hypertension and early occlusive and fibrotic end-stage organ damage owing to vascular lesions in the brain, kidney, and heart. In this study, we evaluated the inflammatory phenotypic changes induced in the arterial wall by chronic N(G)-nitro-L-arginine methyl ester (L-NAME) administration and the effect of an angiotensin II receptor (AT1) antagonist, irbesartan, on these changes. For this purpose, 2 groups of rats received L-NAME in the drinking water (50 mg x kg(-1) x d(-1)) for 2 months. One group received no other treatment and the other was treated with irbesartan (10 mg x kg(-1) x d(-1)). A third group (controls) received neither L-NAME nor irbesartan. After 8 weeks, plasma, aortas, and left ventricles were sampled from all 3 groups. Expression of inducible NO synthase (iNOS) was evaluated at both the mRNA (quantitative reverse transcription-polymerase chain reaction) and the protein (Western blot and immunohistochemistry) level in the aorta. Expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was evaluated by reverse transcription-polymerase chain reaction, Western immunoblotting, and immunohistochemistry; inflammatory cell infiltration by immunohistochemistry; and fibrosis by Sirius red staining. Chronic L-NAME administration induced the expression of iNOS in the aorta, which was localized in smooth muscle cells as shown by immunohistochemistry and NADPH diaphorase activity. ICAM-1 and VCAM-1 expression was also increased in aortas of L-NAME-treated rats. These phenotypic changes of the vascular wall were associated with inflammatory cell infiltration and fibrosis in the heart. All of these pathological phenomena were prevented by the angiotensin II antagonist irbesartan. The proinflammatory phenotypic changes of the vascular wall induced by blockade of NOS activity could be involved in the interaction between endothelial dysfunction and the development of arteriosclerosis.
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PMID:Chronic blockade of NO synthase activity induces a proinflammatory phenotype in the arterial wall: prevention by angiotensin II antagonism. 974 29

1. The aim of this study was to examine the changes in leukocyte adhesion and leukocyte-induced contraction in balloon-injured rabbit subclavian artery and to correlate these changes with vessel morphology and expression of adhesion molecules on the injured arteries. 2. Rabbits were anaesthetized and their left subclavian arteries were injured by balloon inflation and withdrawal followed by sacrifice at 2, 24, 48 h or 8 days after injury. The left and right subclavian arteries were removed and leukocytes were isolated from autologous rabbit blood. Leukocyte-induced contraction was measured in 5-HT precontracted artery rings and leukocyte adhesion was measured using (51)Cr-labelled leukocytes. Immunocytochemistry using paraffin-embedded tissue was employed to detect changes in the expression of adhesion molecules on injured arteries. 3. Autologous leukocytes caused a contraction of rabbit subclavian artery rings, which was prevented by L-NAME (10(-3) M). Balloon-induced injury abolished the contractile response to leukocytes, which correlated with loss of carbachol-induced relaxation 4. Balloon injury markedly enhanced the adhesiveness of the subclavian artery for leukocytes, most notably at 24 and 48 h after injury (1.7 and 1.8 fold respectively). Increased leukocyte adhesion at these two time points correlated with an upregulation of E-selectin, P-selectin and VCAM-1 expression on the remaining endothelium of the injured artery. 5. Vessel morphology revealed that balloon inflation had induced an infiltration of inflammatory cells into the vessel wall, the greatest increase being seen at 24 h after injury. 6. It is concluded that an increase in the expression of E-selectin, P-selectin and VCAM-1 following balloon-induced injury leads to enhanced leukocyte adhesion and migration into the injured vessel.
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PMID:Correlation of leukocyte adhesiveness, adhesion molecule expression and leukocyte-induced contraction following balloon angioplasty. 1078 Oct 3

We have previously shown that circulating intravascular cells generally arrest by mechanical restriction in the hepatic sinusoids, causing rapid release of nitric oxide (NO) which is cytotoxic to these cells and inhibits their growth into metastatic tumours. Here, we present evidence that these NO-dependent cytotoxic mechanisms are susceptible to upregulation by lipopolysaccharide (LPS). Five x 10(5) fluorescently labelled melanoma cells were injected into the mesenteric vein of C57BL/6 mice to effect their localisation in the hepatic microvasculature. Test mice were then given 1 mg/kg LPS intraperitoneally (i.p.) to activate the microvascular cells. By electron paramagnetic resonance (EPR) spectroscopy, the expression of NO in the liver was significantly increased by 8 h in the LPS-treated mice. The non-selective NO synthase inhibitor L-NAME inhibited the induction of NO by LPS, while its inactive enantiomer D-NAME had no significant effect. Using immunohistochemistry (IHC), iNOS-positive microvascular cells were detected in the terminal portal venule (TPV) region of the liver 8 h after LPS stimulation. LPS treatment also increased the retention of melanoma cells in the liver between 8 and 24 h, especially in the TPV region. Eight hours after cell injection, local expression of VCAM-1 and ICAM-1 was detected by double-label immunohistochemistry at the sites of tumour cell arrest. Expression of these adhesion molecules was enhanced in mice treated with LPS. Using flow cytometry, 98% of the B16F1 melanoma cells expressed VLA-4, the counter receptor of VCAM-1, and approximately 1.5% expressed LFA-1, the counter receptor of ICAM-1. LPS did not significantly alter the expression of either counter receptor on melanoma cells in vitro or in vivo. By DNA end-labelling, the rates of melanoma cell apoptosis were significantly increased from 8 to 24 h in the TPV region (but not in the sinusoids) of LPS-treated mice. Fourteen days after tumour cell injection, the LPS-treated mice had a significantly smaller hepatic metastatic tumour burden than the control mice. These data suggest that LPS can inhibit the metastasis of melanoma cells in the liver by inducing the expression of NO and adhesion molecules by the hepatic endothelium. The induction of iNOS and the inducible cytotoxic effect of LPS appear to be primarily located within the TPV region of the liver acinus.
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PMID:Regulation of B16F1 melanoma cell metastasis by inducible functions of the hepatic microvasculature. 1204 14

Nitric oxide (NO) is widely known to inhibit platelet and leukocyte adhesion to endothelium through its regulatory effect on adhesion molecule expression. The objective of the present study was to investigate if NO affects the cytoadherence of Plasmodium falciparum-infected erythrocytes (IRBCs) to human microvascular endothelium (HDMECs) under flow conditions in vitro. The effect of endogenous NO was studied using the NO synthase inhibitor L-N(G)-nitro-arginine-methyl-ester (L-NAME). Treatment of HDMECs with 3 mmol/L of L-NAME for 4 hours significantly enhanced IRBC adhesion and the effect could be reversed by an anti-P-selectin but not an anti-VCAM-1 antibody. The effect of exogenous NO on cytoadherence was studied by using the NO donor 3-(2-hydroxy-2-nitroso-1-propylhydrazino)-1-propanamine (PPN). PPN (300 micro mol/L) treatment reduced the number of adherent IRBCs on resting HDMECs by down-regulating basal ICAM-1 expression, and on tumor necrosis factor-alpha-stimulated HDMECs by inhibition of VCAM-1 induction and down-regulation of ICAM-1 expression. The inhibitory effect of PPN on tumor necrosis factor-alpha-induced VCAM-1 expression at 24 hours was evident when the NO donor was added for as short as 2 hours. These findings suggest that NO may be protective against P. falciparum infection by inhibiting cytoadherence, and underscore the therapeutic potential of NO in the treatment of severe falciparum malaria.
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PMID:Anti-adhesive effect of nitric oxide on Plasmodium falciparum cytoadherence under flow. 1270 49

Chronic inhibition of nitric oxide (NO) synthesis by administration of high dose of N(G)-nitro-L-arginine methylester (L-NAME) induces vascular inflammation and subsequent atherosclerosis. We aimed to investigate whether the methanol extract of Sorbus commixta cortex (MSC) is able to prevent inflammatory process in a rat model of L-NAME-induced atherosclerosis. Chronic treatment with low or high doses of MSC prevented the L-NAME-induced increase in monocyte chemoattractant protein-1 (MCP-1) and nuclear factor-kappaB (NF-kappaB) p65 expressions as well as adhesion molecules including intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in aorta. In addition, increased endothelin-1 (ET-1) and angiotensin converting enzyme (ACE) expressions and decreased endothelial cell NO synthase (ecNOS) expression in aorta from L-NAME treated group was reversed by treatment with MSC. From the histological examination, aortic segment from the L-NAME-treated rats revealed a thickening of intima and media, which was ameliorated by treatment with MSC. In conclusion, our results indicate that MSC can prevent atherosclerosis by inhibiting vascular over-expressions of vasoactive materials, pro-inflammatory transcription factor, and adhesion molecules and by augmenting ecNOS in chronic L-NAME-treated rat model.
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PMID:Effect of methanol extract of Sorbus cortex in a rat model of L-NAME-induced atherosclerosis. 1599 6

Vasorelaxant and anti-inflammatory effects of a 1,2,3,4,6-penta-O-galloyl-beta-d-glucose (PGG) isolated from the root barks of Paeonia suffruticosa and possible mechanisms responsible were investigated. PGG induced a concentration-dependent relaxation of the phenylephrine-precontracted rat aorta. This effect disappeared with the removal of functional endothelium. Pretreatment of the aortic tissues with either N(G)-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4]-oxadiazole-[4,3-alpha]-quinoxalin-1-one (ODQ) inhibited the relaxation induced by PGG. Incubation of human umbilical vein endothelial cells (HUVECs) or carotid arteries isolated from rats with PGG increased the production of cGMP in a dose-dependent manner, but this effect was blocked by pretreatment with L-NAME and ODQ, respectively. PGG treatment attenuated tumor necrosis factor-alpha (TNF-alpha)-induced nuclear factor-kappaB (NF-kappaB) p65 translocation in human umbilical vein endothelial cells. In addition, PGG suppressed the expression levels of adhesion molecules including intracellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) induced by TNF-alpha. TNF-alpha-induced monocyte chemoattractant protein-1 (MCP-1) expression was also attenuated by addition of PGG. PGG treatment inhibited cellular adhesion of U937 cells onto human umbilical vein endothelial cells induced by TNF-alpha. Taken together, the present study suggests that PGG dilates vascular smooth muscle and suppresses the vascular inflammatory process via endothelium-dependent nitric oxide (NO)/cGMP signaling.
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PMID:Vasodilatory and anti-inflammatory effects of the 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG) via a nitric oxide-cGMP pathway. 1625 26

While conducting an in vitro screen of various medicinal plant extracts, an aqueous extract of rhubarb (Rheum undulatum L, AR) was found to exhibit a distinct vasorelaxant activity. AR induced a concentration-dependent relaxation of the phenylephrine-precontracted aorta. This effect disappeared with the removal of functional endothelium. Pretreatment of the aortic tissues with N(G)-nitro-L-arginine methyl ester (L-NAME), methylene blue, or 1H-[1,2,4]-oxadiazole-[4,3-alpha]-quinoxalin-1-one (ODQ) inhibited the relaxation induced by AR. Incubation of human umbilical vein endothelial cells (HUVECs) with AR increased the production of cGMP in a dose-dependent manner, but this effect was blocked by pretreatment with L-NAME and ODQ, respectively. AR treatment attenuated TNF-alpha-induced NF-kappaB p65 translocation in HUVECs in a dose-dependent manner. In addition, AR suppressed the expression levels of adhesion molecules including ICAM-1 and VCAM-1 induced by TNF-alpha in HUVECs. TNF-alpha-induced MCP-1 expression was also attenuated by the addition of AR. This attenuation was blocked by pretreatment with either L-NAME or ODQ. AR treatment inhibited cellular adhesion of U937 cells onto HUVECs induced by TNF-alpha. Taken together, the present study suggests that AR dilates vascular smooth muscle and suppresses the vascular inflammatory process via endothelium-dependent NO/cGMP signaling.
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PMID:Vasodilatory and anti-inflammatory effects of the aqueous extract of rhubarb via a NO-cGMP pathway. 1626 57

Long-acting dihydropyridine calcium channel blockades have been shown to limit the progression of atherosclerosis and decrease the incidence of cardiovascular events in humans and animals. To investigate the vasoprotective effects beyond the blood pressure-lowering effects of these agents, amlodipine (20 mg/kg/ day) and manidipine (10 mg/kg/day) were administered by gavage to N(G)-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats for 2 weeks. L-NAME treatment (0.7 mg/ml in drinking water) significantly decreased the gene and protein expression of endothelial nitric oxide synthase (eNOS) and increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, vascular cell adhesion molecule-1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1) mRNA levels in the aorta, as determined by Western blotting and reverse transcription (RT)-polymerase chain reaction (PCR). Amlodipine and manidipine normalized the decreased expression of eNOS gene and protein, and attenuated the overexpression of NADPH oxidase, VCAM-1, and MCP-1 mRNA. Furthermore, amlodipine and manidipine prevented the L-NAME-induced increase in the angiotensin converting enzyme (ACE) mRNA content, thereby restoring control levels in the aorta. On the other hand, hydralazine treatment had no such effect in L-NAME treated rats. Furthermore, the increased expression of manganese superoxide dismutase (Mn-SOD) by L-NAME treatment was not affected by amlodipine, manidipine, or hydralazine. We concluded that the direct anti-inflammatory and antioxidative effects of calcium channel blockades in the aorta of rats with L-NAME-induced hypertension were not likely to have been mediated by the blood pressure-lowering action of these agents, but instead these beneficial effects appear to have been mediated by an augmentation of eNOS expression and by the inhibition of the expression of ACE.
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PMID:Calcium channel blockades exhibit anti-inflammatory and antioxidative effects by augmentation of endothelial nitric oxide synthase and the inhibition of angiotensin converting enzyme in the N(G)-nitro-L-arginine methyl ester-induced hypertensive rat aorta: vasoprotective effects beyond the blood pressure-lowering effects of amlodipine and manidipine. 1639 74

Oxidative modification of LDL accumulated in the subendothelial space is a critical step in atherogenesis. Mouse strains C57BL/6 (B6) and BALB/c differ markedly in atherosclerosis susceptibility. We sought to determine whether variation of endothelial cells in the capacity to oxidize LDL or in response to minimally modified LDL (MM-LDL) constitutes a genetic component in atherosclerosis. LDL oxidation was assessed by measuring thiobarbituric acid-reactive substance (TBARS) production. Responses to MM-LDL were evaluated by examining induction of monocyte chemotactic protein-1, macrophage-colony stimulating factor, and vascular cell adhesion molecule-1. Both strains exhibited comparable endothelial responses to MM-LDL, whereas BALB/c mice had an increased rate of oxidizing LDL compared with B6 mice. To examine whether endothelial nitric oxide synthase (eNOS) contributed to the difference in LDL oxidation, cells were incubated with native LDL in the presence or absence of N(Omega)-nitro-l-arginine methyl ester (l-NAME), a specific NOS inhibitor. Although l-NAME significantly inhibited endothelial cell-mediated LDL oxidation, it failed to abolish the difference between the strains. In contrast, Baicalein, a specific 12/15 lipoxygenase inhibitor, abolished the difference in LDL oxidation. Thus, the paradoxical increase in LDL oxidation by endothelial cells is attributable to higher oxidant activity of 12/15-lipoxygenase in BALB/c mice and endothelial cells appear unlikely to be a source of the resistance to atherosclerosis.
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PMID:Paradoxical increase in LDL oxidation by endothelial cells from an atherosclerosis-resistant mouse strain. 1691 36


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