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)

The protective effect of melatonin on lipopolysaccharide (LPS)-induced oxidative damage in phenobarbital-treated rats was measured using the following parameters: changes in total glutathione (tGSH) concentration, levels of oxidized glutathione (GSSG), the activity of the antioxidant enzyme glutathione peroxidase (GSH-PX) in both brain and liver, and the content of cytochrome P450 reductase in liver. Melatonin was injected intraperitoneally (ip, 4mg/kg BW) every hour for 4 h after LPS administration; control animals received 4 injections of diluent. LPS was given (ip, 4 mg/kg) 6 h before the animals were killed. Prior to the LPS injection, animals were pretreated with phenobarbital (PB), a stimulator of cytochrome P450 reductase, at a dose 80 mg/kg BW ip for 3 consecutive days. One group of animals received LPS together with Nw-nitro-L-arginine methyl ester (L-NAME), a blocker of nitric oxide synthase (NOS) (for 4 days given in drinking water at a concentration of 50 mM). In liver, PB, in all groups, increased significantly both the concentration of tGSH and the activity of GSH-PX. When the animals were injected with LPS the levels of tGSH and GSSG were significantly higher compared with other groups while melatonin and L-NAME significantly enhanced tGSH when compared with that in the LPS-treated rats. Melatonin alone reduced GSSG levels and enhanced the activity of GSH-PX in LPS-treated animals. Additionally, LPS diminished the content of cytochrome P450 reductase with this effect being largely prevented by L-NAME administration. Melatonin did not change the content of P450 either in PB- or LPS-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Melatonin administration prevents lipopolysaccharide-induced oxidative damage in phenobarbital-treated animals. 759 65

These studies were performed to determine if the effects of angiotensin II infusion on the development of cardiac fibrosis could be modified by the chronic inhibition of nitric oxide synthase activity. NG-nitro-L-arginine-methyl ester (L-NAME) was administered to adult Wistar rats in drinking water (40 mg/kg per d). Although blood pressure was maintained at hypertensive levels after 2 wk, cardiac hypertrophy or fibrosis did not occur. Angiotensin II, given for 3 d at a dose which induced little or no blood pressure elevation and minimal if any fibrosis, caused significant fibrosis when given to a rat pretreated for 2 wk with L-NAME. This marked fibrosis did not occur if angiotensin II was given shortly after L-NAME treatment was begun or briefly after discontinuation of L-NAME. The fibrosis that occurred with combined treatment was characterized by increased immunodetectable fibronectin, the presence of inflammatory cells within interstitial and perivascular regions, and increased steady state mRNA levels for matrix genes and atrial natriuretic protein. The data indicated a regulatory role for nitric oxide in modulating the angiotensin II-induced cardiac fibrosis and suggest a potentially important autocrine or paracrine role for nitric oxide in fibroblast proliferation.
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PMID:Angiotensin II-induced cardiac fibrosis in the rat is increased by chronic inhibition of nitric oxide synthase. 759 36

1. The effects of administering 3 mg ml-1 NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO), on the uptake of low density lipoprotein (LDL), fibrinogen and blood pressure were determined in conscious, unrestrained, cannulated normotensive and spontaneously hypertensive (SHR) Wistar rats. 2. The uptake of LDL and fibrinogen, labelled respectively with 125I or 131I via the adduct tyramine cellobiose ([125I]TC-LDL and [131I]TC-fibrinogen), were compared in aortic walls, heart, skeletal muscle, lung, liver, kidney and adrenal during the final 24 h of 6 days' administration of L-NAME in the drinking water. 3. In control normotensive rats, the systolic blood pressure did not change significantly over 6 days, while administration of L-NAME in normotensive rats increased the blood pressure progressively and significantly to about 170 mmHg over the same period. 4. In normotensive rats L-NAME increased significantly the uptake of both LDL and fibrinogen by aortic walls and heart, but not by muscle, lung, liver, kidney and adrenal. 5. The blood pressure in SHR was about 170 mmHg before administration of L-NAME and did not increase significantly after 6 days of treatment. In these rats the uptake of LDL or of fibrinogen was increased only in the heart but not in aortic walls nor in any of the other organs. 6. In normotensive rats the increase in blood pressure caused by inhibition of NO generation was associated with increases in the uptake of the atherogenic plasma proteins LDL and fibrinogen by the wall of the aorta and by the heart but not by the skeletal muscle, lung, liver, kidney and adrenal. The slightly higher blood pressure of SHR treated with L-NAME was not associated with increased uptake of LDL or fibrinogen by aorta nor by any organ except heart. Thus, while in normotensive rats the increase in blood pressure caused by inhibition of NO generation was associated with increase in the uptake of atherogenic plasma proteins LDL and fibrinogen by the wall of the aorta and by the heart, in SHR which showed uptakes similar to the normotensive animals, the non-significant increase in blood pressure induced by inhibition of NO generation was not associated with increased uptake of LDL or fibrinogen in any organ except the heart.7. These results are consistent with effects, demonstrated earlier, of infusing the pressor agents noradrenaline, adrenaline and angiotensin II, which produce increases in uptake of LDL and fibrinogen by aortic wall, whereas this is not so in spontaneously hypertensive rats.
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PMID:Effect of inhibition of nitric oxide synthesis on the uptake of LDL and fibrinogen by arterial walls and other organs of the rat. 760 53

Previous studies have demonstrated that an acute intravenous administration of nitro-L-arginine methyl ester (L-NAME) causes a sustained hypertension and widespread vasoconstriction. However, little information is available regarding the chronic effect of L-NAME on circulatory hemodynamics. Therefore, the purpose of the present study was to characterize both the systemic and regional hemodynamics after the chronic inhibition of endothelium-derived nitric oxide in male Sprague Dawley rats. The rats were divided into two groups: control (n = 8) and L-NAME (n = 8). The rats in the control group received only tap water and the rats in the L-NAME group received oral L-NAME solution at a dose of 0.1 mg/mL in the drinking water ad libitum. Four weeks after L-NAME or tap water treatment the rats were anesthetized with inactin, and mean arterial blood pressure, cardiac output, and individual organ flows were measured. Cardiac output and individual organ flows were measured using radioactive microspheres. Chronic administration of L-NAME resulted in a significant increase in mean arterial blood pressure from a control value of 118 +/- 4 mm Hg to 174 +/- 8 mm Hg (P < .01). Cardiac output decreased from a control value of 29 +/- 2 mL/min/100 g to 20 +/- 2 mL/min/100 g (P < .01) and total peripheral resistance increased from a control value of 4.3 +/- 0.3 mm Hg/mL/min/100 g to 9.7 +/- 1.4 mm Hg/mL/min/100 g (P < .01). In addition, chronic L-NAME treatment resulted in a widespread vasoconstriction and decrease in regional blood flows.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Overall hemodynamic studies after the chronic inhibition of endothelial-derived nitric oxide in rats. 761 48

We investigated the role of endogenous nitric oxide, kinins, and prostaglandins in the vasodepressor and renal excretory effects of the angiotensin II receptor antagonist losartan and the angiotensin-converting enzyme inhibitor ramipril administered for 1 week to spontaneously hypertensive rats. To this end, either losartan (10 mg/kg per day) or ramipril (2.5 mg/kg per day) was administered in drinking water with or without simultaneous administration of (1) the nitric oxide synthesis inhibitor Ng-nitro-L-arginine methyl ester (L-NAME, 6 mg/kg per day), (2) the cyclooxygenase inhibitor indomethacin (5 mg/kg per day), (3) the bradykinin B2 receptor antagonist Hoe 140 (0.5 mg/kg per day SC), or (4) L-NAME plus indomethacin. Both losartan and ramipril significantly reduced blood pressure as measured by the tail-cuff method. L-NAME increased blood pressure when administered solely or in combination with losartan. However, L-NAME attenuated the hypotensive effect of ramipril. Indomethacin did not affect blood pressure but it reduced the antihypertensive action of losartan and ramipril. Indomethacin administration did not potentiate the increase in blood pressure induced by L-NAME. However, the concurrent administration of both inhibitors almost totally blunted the vasodepressor action of ramipril. By contrast, losartan administration in the presence of L-NAME and indomethacin increased blood pressure to a level similar to that after losartan plus L-NAME. Hoe 140 did not modify either blood pressure or the hypotensive effects of losartan or ramipril. Increases in diuresis and water intake were observed during ramipril administration. Both effects were blunted only with the concurrent administration of L-NAME and indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitric oxide and prostaglandins in the prolonged effects of losartan and ramipril in hypertension. 763 31

Nitric oxide synthesis appears to be elevated in inflammatory bowel disease, but little is known about the contribution of nitric oxide to the pathophysiological process. To address this issue, we included the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) in the drinking water (10 or 100 micrograms/ml) of guinea pigs immediately after induction of ileitis by intraluminal trinitrobenzenesulfonic acid (TNBS 30 mg/kg in 50% ethanol). Guinea pigs were sacrificed after 7 days of this ad libitum treatment. Control groups received either intraluminal TNBS, saline or ethanol (TNBS vehicle) without L-NAME or TNBS + D-NAME (100 micrograms/ml), the inactive enantiomer. Immediately before sacrifice, guinea pigs were anesthetized and saline was administered intraluminally at the site of TNBS or saline administration and then withdrawn after 30 min. Change in lavage volume and lavage protein and nitrite levels were measured, as well as tissue myeloperoxidase and bowel wall thickness (weight/length). TNBS administration resulted in an increase in tissue thickness, myeloperoxidase and lavage protein and nitrite levels over sham controls. Oral L-NAME prevented these responses. D-NAME was ineffective with the exception of tissue thickness. The change in intestinal lavage fluid volume indicated that reabsorptive processes dominated in the sham and TNBS + L-NAME groups, and secretory responses predominated in TNBS and TNBS + D-NAME animals. In contrast to TNBS-induced ileitis, L-NAME (100 micrograms/ml, p.o., 7 days) administration to intact animals resulted in a local inflammatory response (i.e., increased myeloperoxidase activity and a fluid secretory response).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Amelioration of chronic ileitis by nitric oxide synthase inhibition. 767 45

To determine whether inhibition of generation of endothelium-derived relaxing factor or nitric oxide (NO) resulted in elevated blood pressure and its effect on resistance arteries, rats were offered NG-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NO synthase, in their drinking water. Blood pressure (BP) rose slightly from 100 +/- 2 mmHg in controls to 130 +/- 5 mmHg with 25 mg/Kg L-NAME per day and to 173 +/- 9 mmHg with 100 mg/Kg per day for 2 1/2 to 4 weeks. Rats were studied after 1-2 weeks of hypertension (BP > 150 mmHg). The concentration of cyclic guanosine monophosphate, the intracellular second messenger of NO, was significantly depressed in aorta and in the mesenteric vascular bed in L-NAME-treated rats. Mesenteric resistance arteries studied on a wire-myograph exhibited similar external and lumen diameters, whereas media width and media/lumen ratio were greater (p < 0.01). Cross-sectional area of the media was similar. Active wall tension in response to norepinephrine tended to be greater in blood vessels from L-NAME-treated rats, while responses to vasopressin and endothelin-1 were unaltered. Sensitivity to norepinephrine was significantly enhanced in L-NAME-treated rats (p < 0.001), while that to endothelin-1 and arginine8 vasopressin was similar. In conclusion, administration of an NO synthase inhibitor produces hypertension, with exaggerated media/lumen ratio in resistance arteries and enhancement of response to norepinephrine, which together with decreased NO generation may contribute to elevation of blood pressure.
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PMID:Effect of hypertension induced by nitric oxide synthase inhibition on structure and function of resistance arteries in the rat. 768 50

Blockade of the renin-angiotensin system was studied in male Sprague-Dawley rats during long-term inhibition of nitric oxide synthase. Nitro-L-arginine-methyl ester (L-NAME) was placed in the drinking water for 4 weeks (approximately 100 mg/kg per day). Separate groups of rats were coadministered the angiotensin II antagonist A-81988 in the drinking water ranging from approximately 0.001 to 1 mg/kg per day. Control groups received only tap water or A-81988 alone. Each week, rats were placed in metabolic cages, and tail-cuff blood pressures and blood samples were taken. L-NAME produced a sustained elevation in tail-cuff pressure that was completely prevented by A-81988. No changes in creatinine clearance, sodium excretion, plasma creatinine concentration, or blood urea nitrogen were observed. Food and water intakes were identical in all groups. Water excretion was significantly increased in L-NAME-treated animals regardless of additional inhibitor treatment, suggesting a possible role for nitric oxide synthase in the control of water excretion; this effect was independent of blood pressure. Although less potent than A-81988, the angiotensin II antagonist losartan and the angiotensin converting enzyme inhibitor enalapril also blocked L-NAME-induced hypertension. In a separate series of experiments, rats were not given A-81988 until 2 weeks after hypertension had fully developed in L-NAME-treated rats. Within 1 week of treatment with the angiotensin II antagonist, tail-cuff pressure returned to normal. We conclude from these studies that long-term inhibition of endogenous nitric oxide production produces an angiotensin II-dependent form of hypertension.
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PMID:Angiotensin blockade reverses hypertension during long-term nitric oxide synthase inhibition. 768 26

1. The effects of acute inhibition of nitric oxide (NO) synthase on cardiovascular responses to vasodilator challenges have already been described. We now report the responses to vasodilators during and after chronic NO synthase inhibition. 2. In conscious Brattleboro rats, the regional haemodynamic effects of 3 min infusions of acetylcholine (4 micrograms min-1), sodium nitroprusside (15 micrograms min-1) or adrenaline (0.2 micrograms min-1) were assessed (from areas under or over curves (AUC, AOC)) under control conditions, 6 and 72 h after the addition of the NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA) to the drinking water (1 mg ml-1), and 6, 24 and 48 h after the withdrawal of L-NMMA. In a separate group of Brattleboro rats, responses to acetylcholine, sodium nitroprusside and adrenaline were assessed before and 6 h after the onset of oral ingestion of the more potent nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 0.05 mg ml-1). 3. Acetylcholine caused renal vasodilation (87 +/- 11 units) and mesenteric vasoconstriction (-31 +/- 5 units), sodium nitroprusside caused vasodilatation in renal (96 +/- 12 units), mesenteric (222 +/- 13 units) and hindquarters (49 +/- 15 units) vascular beds, whereas adrenaline caused hindquarters vasodilatation (92 +/- 8 units). Seventy two h after the onset of oral ingestion of L-NMMA, acetylcholine had a decreased renal vasodilator (59 +/- 9 units) effect, sodium nitroprusside had an increased renal vasodilator (142 +/- 23 units) action, while adrenaline had a decreased hindquarters vasodilator (55 +/- 6 units) influence. Twenty four h after withdrawal of L-NMMA, the renal vasodilator effect of acetylcholine was greater than the control response (106 +/- 14 units), but the regional haemodynamic effects of sodium nitroprusside and adrenaline were not different from those under control conditions. Hence, the increased renal vasodilator response to acetylcholine was probably due to changes in muscarinic receptor-mediated mechanisms rather than to any increase in guanylyl cyclase or its sensitivity to NO.
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PMID:Effects of chronic treatment with nitric oxide synthase inhibitors on regional haemodynamic responses to vasodilators in conscious Brattleboro rats. 768 4

Intracerebroventricular (i.c.v.) administration of NG-monomethyl-L-arginine monoacetate (NMMA; 500 micrograms; 402 mM) and NG-nitro-L-arginine methyl ester (NAME; 270 micrograms; 200 mM), inhibitors of nitric oxide synthase, enhanced the rise in oxytocin but not vasopressin levels in plasma of conscious rats following 24 h of water deprivation. This effect of NMMA occurred by 10 min after administration, reached its peak at 15 min and decreased by 20 min. Daily administration of lower doses (50 micrograms and 0.5 microgram/5 microliter, i.c.v.) of another inhibitor of nitric oxide synthase, NG-nitro-L-arginine, just before and after 24 h of water deprivation and in control animals treated similarly were without effect on either vasopressin or oxytocin levels. Nitric oxide, therefore, attenuates preferentially the release of oxytocin during dehydration.
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PMID:Central inhibition of nitric oxide synthase preferentially augments release of oxytocin during dehydration. 768 65


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