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)

This study was designed to determine whether the kallikrein-kinin system exerts a protective action in hypertension induced by chronic inhibition of nitric oxide synthase. N omega-nitro-L-arginine methyl ester (L-NAME, 40 mg/100 ml water) was given orally to Sprague-Dawley rats, while controls received regular tap water. Hepatic kininogen mRNA levels in the L-NAME-treated group were 2.9- and 2.5-fold higher at 3 and 4 wk, respectively, compared with control rats, whereas kallikrein-binding protein (KBP) mRNA levels were 82% and 45% of the values found in control rats at 3 and 4 wk, respectively. There was no significant change in hepatic alpha 1-antitrypsin mRNA levels under the same conditions. At 3 and 4 wk post L-NAME treatment, renal kallikrein mRNA levels were 2.5- and 3.4-fold higher than in controls, whereas renal beta-actin mRNA levels were similar between groups. Changes in the transcript levels of renal kallikrein, kininogen, and KBP were consistent with their protein levels. Immunoreactive total kininogen and low-Mr kininogen levels in sera and tissue kallikrein levels in kidney were significantly higher in the L-NAME-treated group, whereas KBP levels in the circulation were lower compared with controls. Systolic blood pressure was increased by 58 +/- 4 mmHg after 4 wk of L-NAME treatment. This effect was enhanced in rats given L-NAME in combination with HOE-140, a bradykinin B2-receptor antagonist, at the dose of 100 micrograms/day ip (79 +/- 5 vs. 58 +/- 4 mmHg, P < 0.05). This difference was confirmed by direct measurement of mean blood pressure (MBP). An intra-arterial bolus injection of 200 ng bradykinin significantly decreased MBP of L-NAME-treated rats, and this effect was blunted in the group treated with the bradykinin antagonist (-29 +/- 3 vs. -9 +/- 2 mmHg, P < 0.01). These results suggest that enhanced kallikrein and kininogen synthesis may have a protective role against the cardiovascular effects induced by chronic inhibition of nitric oxide synthesis.
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PMID:Differential regulation of kallikrein, kininogen, and kallikrein-binding protein in arterial hypertensive rats. 876 Feb 46

We investigated the involvement of nitric oxide in transmural jejunal alterations induced by Trichinella spiralis (T. spiralis) infection in rats. Rats were gavaged with either saline or T.spiralis larvae, and, 1 h later, rats were treated orally with water, NG-nitro-L-arginine methyl ester (L-NAME; 30 mg/kg), or NG-nitro-D-arginine methyl ester (D-NAME; 30 mg/kg) on a daily basis. Although not observed in jejunum from uninfected rats, inducible nitric oxide synthase (iNOS) mRNA was present in the mucosa and neuromuscular layers of jejunum from T. spiralis-infected rats. On day 6, T. spiralis-infected rats had a 6-fold decrease in transmural nitric oxide synthase activity, an 11-fold increase in plasma nitrite, and a 7-fold elevation in transmural myeloperoxidase (MPO) activity compared with uninfected controls. Intestinal smooth muscle cell hyperplasia and hypertrophy were only detected in the infected rats. L-NAME, but not D-NAME, treatment of infected rats for 6 days caused a pronounced increase in transmural iNOS mRNA expression, coinciding with significantly increased mucosal nitric oxide synthase activity. T. spiralis numbers in L-NAME-treated rats were significantly lower compared with the other two infected groups although L-NAME had no direct effect on T. spiralis viability in vitro. Furthermore, L-NAME treatment significantly reduced plasma nitrite and jejunal MPO but not intestinal smooth muscle cell hyperplasia or hypertrophy. In contrast, D-NAME treatment of infected rats significantly enhanced intestinal smooth muscle hyperplasia and hypertrophy. Taken together, these results suggest that alterations in the T. spiralis-infected jejunum are mediated, in part, by a suppression of nitric oxide synthase activity in the inflamed jejunum.
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PMID:Effects of oral L-NAME during Trichinella spiralis infection in rats. 877 50

Nitric oxide has been suggested to be an essential mediator of pressure natriuresis. To investigate this hypothesis, the effect of acute or chronic inhibition of nitric oxide synthase on pressure natriuresis and renal interstitial hydrostatic pressure was studied in anesthetized Sprague-Dawley rats with fixed neural and hormonal influences on the kidney. Both acute infusion (10 micrograms.kg-1.min-1 iv) and chronic administration (50 mg.kg-1.day-1 for 7 days in drinking water) of NG-nitro-L-arginine methyl ester (L-NAME) resulted in significantly increased mean arterial pressure, a 30% decrease in renal blood flow, and no change in glomerular filtration rate when compared with values in control rats. Pressure-diuresis, pressure-natriuresis, and pressure-fractional sodium excretion curves in L-NAME-treated rats were shifted to a higher pressure (by approximately 25 mmHg) when compared with those in control rats. The relationship between renal artery pressure and renal interstitial hydrostatic pressure was shifted similarly in L-NAME-treated rats. Acute administration of L-arginine completely reversed the renal effects of chronic L-NAME. These data indicate that, at the doses used in this study, both acute and chronic inhibition of nitric oxide synthase decreased the ability of the kidney to excrete sodium at least in part by a hemodynamic mechanism leading to an increased filtration fraction and a decreased renal interstitial pressure. The parallel shift of the pressure-natriuresis curve to a higher pressure suggests that nitric oxide is an important modulator but not an essential mediator of the pressure natriuresis.
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PMID:Pressure natriuresis following acute and chronic inhibition of nitric oxide synthase in rats. 877 81

1. The aim of this study was to investigate whether nitric oxide (NO) and/or vasodilator prostaglandins (PGs) are involved in the sympathoinhibitory effects exerted by losartan versus the vascular responses elicited by spinal cord electrical stimulation (SCS) in pithed spontaneously hypertensive rats (SHRs). 2. SHRs were given orally and for 8 days either losartan (10 mg kg-1 daily) or distilled water (controls). After pithing, blood pressure, heart rate, cardiac output, renal and muscular blood flows (pulsed Doppler technique) and the corresponding vascular resistance values were measured or calculated at baseline. Then, animals from both groups were given i.v. either saline, or NG-nitro-L-arginine methyl ester (L-NAME, 1 mg kg-1), or diclofenac (4 mg kg-1). Thereafter, haemodynamic parameters were determined in the six subgroups of animals in response (a) to SCS at increasing frequencies, and (b) to a noradrenaline bolus injection. 3. Losartan significantly decreased mean arterial pressure as well as renal and total peripheral resistances. In addition, losartan exhibited strong vascular sympathoinhibitory effects, significantly decreasing the systemic pressor and regional vasoconstrictor responses to SCS, but did not affect those to exogenous noradrenaline. In contrast, SCS-induced tachycardia was not modified by losartan. 4. L-NAME significantly increased total peripheral and regional vascular resistances but did not affect blood pressure and heart rate basal values. L-NAME potentiated the haemodynamic responses to SCS in control and, to a larger extent, in losartan-treated SHRs so that, with the exception of the renal vascular bed, the sympathoinhibitory effects of losartan were attenuated in all vascular beds studied. L-Arginine (300 mg kg-1) caused reversal of L-NAME effects in both control and losartan-treated SHRs. 5. Diclofenac did not affect the basal values of haemodynamic parameters in control and losartan-treated SHRs. Diclofenac potentiated the pressor and vasoconstrictor responses to SCS and to a similar extent, in both control and losartan-treated SHRs, so that the sympathoinhibitory effects of losartan were fully maintained. 6. These results demonstrate that in pithed SHRs: (a) NO but not PGs contribute to the basal vasomotor tone, (b) both NO and PGs attenuate the pressor and vasoconstrictor responses to SCS, (c) NO plays a major role in the vascular sympathoinhibitory effects of losartan, except at the renal level, and (d) endogenous PGs are not involved in these sympathoinhibitory effects.
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PMID:Involvement of nitric oxide, but not prostaglandins, in the vascular sympathoinhibitory effects of losartan in the pithed spontaneously hypertensive rat. 878 85

1. Administration of nitric oxide (NO) synthase inhibitors, such as L-NAME, is associated with an increase in blood pressure and an increase in pressor responsiveness to infused angiotensin II (AngII). The present study was designed to investigate the contribution of changes in the metabolism of AngII to the enhanced pressor response to AngII in the spontaneously hypertensive rat (SHR; 14 weeks old) chronically treated with L-NAME. 2. Group I rats received L-NAME for 7 days (5 mg/kg per day) in their drinking water. Group II rats received water only. On day 7, rats were anaesthetized and metabolic clearance studies were performed. AngII concentrations in plasma and infusate were measured by radioimmunoassay. 3. Urinary NO2 was unchanged after L-NAME treatment, while NO3 decreased compared with control. Mean arterial pressure (MAP) was higher in the L-NAME treated rats than in control. After 30 min infusion of AngII, MAP increased significantly in both groups, although the increase was larger in L-NAME-treated than control rats. The metabolic clearance rate of AngII was significantly lower in L-NAME-treated rats than in the control group. 4. We conclude that chronic NO synthase inhibitors, such as L-NAME, cause a decrease in the rate at which AngII is metabolized. This decrease, in combination with the increase in the number of vascular AngII receptors, may account for the reported increase in pressor responsiveness to infused AngII.
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PMID:Changes in angiotensin II metabolism contribute to the increased pressor response to angiotensin after chronic treatment with L-NAME in the spontaneously hypertensive rat. 880 Jun 1

We addressed the hypothesis that administration of nitric oxide synthase inhibitor, NG -nitro-L-arginine methyl ester (L-NAME) does not result in a sustained suppression of nitric oxide (NO) synthesis, because of a compensatory expression of inducible nitric oxide synthase (iNOS). L-NAME was administered in the drinking water (0.1-1.0 mg/ml) for 7 days to guinea pigs and rats. Nitric oxide synthesis was assessed by [1] ex vivo formation of nitrite in blood vessels and intestine [2] tissue levels of cGMP [3] iNOS gene expression by RT-PCR [4] NADPH diaphorase staining [5] direct assessment of NO release in tissue explants using a microelectrode/electrochemical detection system. Chronic L-NAME administration elevated intestinal cGMP and nitrite levels in guinea pigs (p < 0.05). In rats, intestinal nitrite levels were comparable in control and L-NAME treatment groups, whereas direct assessment of NO release defined a marked increase in the L-NAME group. Chronic L-NAME resulted in an induction of iNOS gene expression in rats and guinea pigs and novel sites of NADPH diaphorase staining in the intestine. We conclude that iNOS expression is responsible for a compensatory increase or normalization of NO synthesis during sustained administration of L-NAME.
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PMID:Failure of L-NAME to cause inhibition of nitric oxide synthesis: role of inducible nitric oxide synthase. 881 57

While essential hypertension may be characterized by insulin resistance, it is unclear which defect is primary. We therefore compared normotensive Sprague-Dawley male rats who drank N-nitro-L-arginine methyl ester (L-NAME, 1 mg/mL in distilled water), with control rats who drank distilled water. Blood pressure was measured noninvasively, weight was controlled by dietary restriction, and glucose tolerance was assessed via oral glucose tolerance tests (OGTT). Blood pressure rose by the second day of L-NAME treatment, and remained elevated throughout the study, in contrast to the rats drinking water (P < .001). Weight rose similarly in both groups. OGTT were performed after 2 weeks of L-NAME. Serum glucose and insulin responses, assessed by two-way ANOVA, were similar in the two groups (P = NS). In summary, L-NAME administration resulted in hypertension, but not a deterioration in glucose tolerance in diet-controlled Sprague-Dawley rats. We conclude that the insulin resistance of some hypertensive states is not the result of hypertension per se, or increased vasoconstriction, such as might result from inhibition of endogenous nitric oxide synthesis, but rather indicates a fundamental metabolic disorder.
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PMID:Oral administration of the nitric oxide biosynthesis inhibitor, N-nitro-L-arginine methyl ester (L-NAME), causes hypertension, but not glucose intolerance or insulin resistance, in rats. 884 69

Oxidative damage in various tissues of LPS-treated rats was studied using the following parameters: changes in reduced (GSH) and oxidized glutathione (GSSG) levels in liver, brain and lens; the activity of glutathione peroxidase (GSH-PX) in both liver and brain; the content of cytochrome P450 reductase in liver. Bacterial LPS was injected i.p. (at a dose of 4 mg/kg BW) 6 h before the animals were killed. One group of rats received N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS) (given for 4 days in the drinking water at a concentration of 50 mM); another group received both L-NAME and LPS. In brain and lens no changes in GSH were observed after either LPS, L-NAME or both. In contrast, GSSG and the GSSG/GSH ratio was significantly higher after LPS. This effect was abolished in the brain by L-NAME treatment. The level of the activity of the antioxidative enzyme GSH-PX in brain was significantly higher after L-NAME in LPS-treated animals. Hepatic GSH-PX activity was enhanced after either LPS, L-NAME or treatment with both substances. Additionally, LPS diminished the level of cytochrome P450 reductase with this effect being largely prevented by L-NAME. The results suggest that GSH, as an endogenous antioxidant, may play a major role in combating toxicity of LPS.
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PMID:Oxidative changes in the liver, brain and lens of lipopolysaccharide-treated rats. 884 34

Flow-induced changes in vessel caliber tend to restore baseline wall shear stress (WSS) and have been reported to be endothelium-dependent. To investigate the role of endothelium-derived nitric oxide (NO) in the adaptive increase in artery diameter in response to a chronic increase in blood flow, an arteriovenous fistula was constructed between the left common carotid artery (CCA) and the external jugular vein in 22 New Zealand White rabbits, and NO synthesis was inhibited in 14 animals by long-term administration of NG-nitro-L-arginine-methyl ester (L-NAME) in drinking water given for 4 weeks. The remaining 8 animals served as controls. Mean arterial blood pressure was not significantly altered by L-NAME treatment (91 +/- 2 in control versus 98 +/- 3 mm Hg in L-NAME-treated rabbits). Blood flow significantly increased in the left CCA in both groups but was lower in L-NAME-treated than control animals (106.1 +/- 10.7 versus 196.2 +/- 32.3 mL/min, P < .003). The diameter of the flow-loaded left CCA also increased significantly in both groups compared with the right CCA (2.15 +/- 0.12 and 2.54 +/- 0.1 mm, respectively, P < .02), but the increase was less in the L-NAME-treated than the control group (3.24 +/- 0.09 and 4.64 +/- 0.17 mm, respectively, P < .0001). The diameter of the anastomosed veins was also increased but to a much lesser degree in L-NAME-treated animals than in controls (4.14 +/- 0.29 versus 7.94 +/- 0.51 mm, P < .0001). As a result of artery enlargement, WSS was normalized in the flow-loaded left CCA of the control group (8.87 +/- 0.77 dynes/cm2) regardless of blood flow values. In L-NAME-treated animals, however, WSS was only partially regulated, the mean value being significantly increased (18.7 +/- 2.2 dynes/cm2, P < .006). Moreover, a highly significant positive correlation between WSS and blood flow was obtained in L-NAME-treated animals (r = .84, P < .0001). We also found remodeling of the artery wall, with a larger increase in the medial cross-sectional area associated with an increased number of smooth muscle cells, in the control group compared with the L-NAME-treated group (0.75 +/- 0.09 versus 0.49 +/- 0.04 mm2 and 4504 +/- 722 versus 2717 +/- 282 cells/mm2, P < .03). We conclude that NO plays a role in the increase of vessel caliber in response to chronic increase in blood flow. As yet unidentified additional metabolic processes appear to be necessary for a complete regulatory response.
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PMID:Role of NO in flow-induced remodeling of the rabbit common carotid artery. 885 22

In both humans and in experimental animals, acute lung injury (ALI) is characterized by the development of pulmonary edema and arterial hypoxemia. It has been reported that the hypoxemia of ALI is related to the failure of those mechanisms that result in the diversion of blood flow away from hypoxic (edematous) lung units to those that are well oxygenated. One such mechanism is hypoxic pulmonary vasoconstriction (HPV). In the pulmonary circulation, endogenous nitric oxide (NO) has been shown to oppose HPV and, thereby, to support blood flow to hypoxic alveoli. In the present work we investigated the hypothesis that, in ALI, endogenous NO, by virtue of its ability to oppose HPV, supports blood flow to hypoxic lung units resulting in increases in venous admixture (Qva/Qt) and decreases in arterial oxygen tension (PaO2). In anesthetized and mechanically ventilated dogs, the intravenous administration of ethchlorvynol (ECV, 15 mg/kg) resulted in an increase in extravascular lung water (EVLW) of 10 +/- 1 ml/kg body wt (p < 0.001) as well as a 120 +/- 45% increase in Qva/Qt (p < 0.01) and a 23 +/- 5% decrease in PaO2 (p < 0.01) (n = 3). L-NAME (1 mg/kg iv, followed by 5 mg/kg/h, iv), administrated 60 min after ethchlorvynol (ECV), prevented entirely the ECV-induced increase in Qva/Qt and fall in PaO2 with minimal effect on EVLW (n = 3). We conclude that, in this model of ALI, endogenous NO is present in the lung and acts to support blood flow to poorly oxygenated lung units resulting, thereby, in reductions in PaO2.
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PMID:Inhibition of nitric oxide synthesis improves arterial oxygenation in ethchlorvynol-induced acute lung injury in dogs. 886 43


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