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)

Rats pretrained in a conditioned avoidance (CAR) paradigm were put on eight potentially addictive drugs in drinking water at two dose levels each. Fluid intake and body weight, monitored during the drugged (addiction) and nondrugged (withdrawal) states, showed drug/dose-dependent fluctuations in most groups. Extinction and relearning trials were spread over both drug and nondrug phases. CAR-performance generally deteriorated in the early drug phase but improved to near normalcy during the late drug and withdrawal phases in all groups except for alcohol and barbiturate-treated one. Excluding amphetamine, low-dose morphine and phenobarbital groups, substantial extinction of CAR occurred during the drug phase only; these three groups, as well as the high-dose alcohol, barbiturates and medazepam ones, showed extinction during the nondrug phase also. The rate and extent of a second-order relearning neither differed significantly between the groups nor was truly contingent upon prior extinction. These results are discussed in the light of state-dependent learning, comparing them with those from another series of rats primarily trained under the influence of these addictive drugs.
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PMID:Conditioned avoidance behavior in pretrained rats intermittently treated with addictive drugs. 123 80

Studies were performed in the opossum to define the role of the L-arginine-nitric oxide (NO) pathway in lower esophageal sphincter (LES) relaxation to swallowing and vagal stimulation in viv and intramural nerve stimulation in vitro. In vivo, L-NAME, a water soluble NO synthase (NOS) inhibitor, caused antagonism of LES relaxation due to reflex-induced swallowing. L-NAME (20 mg/kg i.v.) reduced the amplitude of swallow induced relaxation from 88% to 28%. LES relaxation due to electrical stimulation of peripheral end of decentralized vagus nerve was also antagonized. The effects of L-NAME were reversed by L-arginine, but not by D-arginine. L-NAME treatment did not antagonize LES relaxation to intravenous administration of isoproterenol. In vitro, NO and sodium nitroprusside (SNP) caused a decrease in the sphincter tone. The relaxing effect caused by NO and SNP was not antagonized by tetrodotoxin or omega-conotoxin. Inhibitors of NO synthase, L-NMMA and L-NNA, caused slight increase in the spontaneous resting LES tone and concentration-dependent antagonism of electrical field stimulation (EFS) induced LES relaxation. L-NNA (10(-4)M) abolished EFS induced LES relaxation at low frequencies (less than 5 Hz) and antagonized the relaxation to a value 20% of the control at 20 Hz. The antagonistic action of L-NMMA and L-NNA was unaffected by D-arginine but was reversed by L-arginine. The inhibitory effect of NO, SNP, or two other putative inhibitory neurotransmitters (VIP and CGRP) on the LES was not antagonized by L-NNA. These studies show that inhibitors of NO synthase selectively antagonize LES relaxation to all three modes of intramural inhibitory nerve stimulation including physiological swallowing. These studies suggest that the L-arginine-nitric oxide pathway is involved in physiological relaxation of the LES.
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PMID:Role of nitric oxide in lower esophageal sphincter relaxation to swallowing. 137 90

To evaluate the participation of nitric oxide (NO) on pressure-induced natriuresis in pentobarbital-anesthetized dogs, renal perfusion pressure (RPP) was increased twice from 100 to 150 mmHg before and during the intrarenal administration of an NO-synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), while determining changes in glomerular filtration rate (GFR), renal blood flow (RBF), and urine sodium and water excretion. Before the inhibition of NO, the increase in RPP induced diuresis (5-fold) and natriuresis (4.2-fold) with no change in RBF or GFR. However, the intrarenal infusion of L-NAME (1 microgram.kg-1.min-1) blunted the diuretic and natriuretic responses without altering RBF or GFR. The infusion of the NO synthesis precursor L-arginine prevented the inhibitory effect that L-NAME exerted on the diuretic and natriuretic responses to the increase in RPP. These results indicate that the increase in RPP stimulates NO synthesis and suggest that NO might play an important role in the control of sodium and water excretion during acute changes in RPP.
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PMID:Blockade of pressure natriuresis induced by inhibition of renal synthesis of nitric oxide in dogs. 159 Apr 15

The dose-dependent effects of intravenous infusions of nitric oxide (NO) synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 0.1, 1, 10, and 50 micrograms.kg-1.min-1), were studied in anesthetized rats to determine whether the inhibitory actions of L-NAME are manifested primarily in alterations of renal function or whether they are the consequences of the increase in systemic blood pressure. Mean arterial pressure (MAP) was not altered by the intravenous L-NAME infusions of 0.1 and 1.0 microgram.kg-1.min-1. However, 0.1 microgram.kg-1.min-1 L-NAME induced a 30% decrease in urine flow rate (UV). The administration of 1.0 microgram.kg-1.min-1 L-NAME, in addition to decreasing UV, also decreased urinary sodium excretion (UNaV) and renal plasma flow (RPF). The intravenous L-NAME infusions of 10.0 and 50.0 microgram.kg-1.min-1 intravenous L-NAME infusions of 10.0 and 50.0 microgram.kg-1.min-1 produced significant increases in MAP that reversed the initial fall in UV and UNaV, despite decreasing RPF and glomerular filtration rate (GFR). The administration of L-arginine alone (10 micrograms.kg-1.min-1) did not modify any of the parameters measured, but it effectively prevented all the hemodynamic and renal changes induced by the infusion of 50 micrograms.kg-1.min-1 L-NAME. These results suggest that the decrease in nitric oxide production induced by the intravenous infusion of L-NAME affects renal excretion of sodium and water in the absence of any significant change in blood pressure. At larger doses, L-NAME also produces hypertension that overrides the initial antinatriuretic effect.
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PMID:Effects of NG-nitro-L-arginine methyl ester on renal function and blood pressure. 175 May 17

Homozygous Brattleboro (i.e. vasopressin-deficient) rats were chronically instrumented with pulsed Doppler probes and intravascular catheters to permit continuous monitoring of regional haemodynamics. Over a 9 h period, rats drinking water showed no systematic changes in heart rate or mean arterial blood pressure although renal, mesenteric and hindquarters vascular conductances fell. These changes showed diurnal rhythms, probably related to the nocturnal habits of rats. In separate groups of animals spontaneous oral ingestion of NG-monomethyl-L-arginine (L-NMMA; 1 mg ml-1) or NG-nitro-L-arginine methyl ester (L-NAME; 0.1 mg ml-1) caused marked hypertension but no significant bradycardia. Compared to control animals, rats drinking L-NMMA for 9 h showed significantly greater mesenteric and hindquarters vasoconstrictions, and rats drinking L-NAME showed greater vasoconstrictions in all 3 vascular beds.
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PMID:Regional haemodynamic changes during oral ingestion of NG-monomethyl-L-arginine or NG-nitro-L-arginine methyl ester in conscious Brattleboro rats. 228 51

The variable levels of HbF in sickle cell anemia reflect the heterogeneous genetic mix of the beta s-gene-cluster haplotypes and coinheritance of alpha-thalassemia-2 in American SS patients. Clinical severity is less when the level of HbF reaches 20% or 1.2 g/dl or more. The coinheritance of alpha-thalassemia-2 not only increases the intracellular red cell water but modifies the HbF level in accordance with the beta-cluster haplotype. In general, the SS patient with at least one Senegalese haplotype who does not have a CAR haplotype in trans, has a significantly greater probability of maintaining HbF above 20%. This is in part related to the genetic control of the G gamma HbF locus. Such a patient is protected from arteriolar vasculopathy and subsequent major organ destruction. Much of this but perhaps not all of the better health of patients with a Senegalese haplotype can be attributed to the elevation of G gamma HbF. The coinheritance of alpha-thalassemia-2 further decreases the risk of major morbidity of the soft tissues but increases the risk of avascular necrosis of the bony skeleton. Although these heterozygous Senegal patients are healthier, eventually most, in time, will show the deleterious effect of HbS as retinopathy and avascular necrosis usually beginning after age 30 and sickle nephropathy after age 40. Because of the age-specific effect, the onset of the sickle vasculopathy is delayed by nearly 20 years in the Sen/Ben patient with increased G gamma HbF as compared to those with a CAR haplotype or the homozygous Benin. Lifetime elevation of HbF above 20% modifies the severity of disease expression and provides relative protection to the patient with sickle cell anemia.
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PMID:The influence of fetal hemoglobin on the clinical expression of sickle cell anemia. 247 64

The aim of the present study was to investigate the effects of long-term blockade of nitric oxide synthesis with the L-arginine analogue N omega-nitro-L-arginine methyl ester (L-NAME) for 8 weeks on coronary vascular and myocardial structural changes. Four groups of Wistar-Kyoto rats were studied: those with no treatment, those treated with L-NAME 1 g/L (3.7 mmol/L in drinking water), those treated with L-NAME 0.1 g/L (0.37 mmol/L in drinking water), and those treated with L-NAME 1.0 g/L and hydralazine 120 mg/L (0.6 mmol/L in drinking water). After 8 weeks, the heart was excised, and the degrees of structural changes in coronary arteries (wall-to-lumen ratio and perivascular fibrosis), myocardial fibrosis, and myocyte size were quantified by an image analyzer. Chronic inhibition of nitric oxide synthesis increased arterial pressure compared with control animals. Chronic inhibition of nitric oxide synthesis caused significant microvascular remodeling (increased wall-to-lumen ratio and perivascular fibrosis). Cardiac hypertrophy was also observed after chronic inhibition of nitric oxide synthesis. Coadministration of hydralazine prevented arterial hypertension but did not affect microvascular remodeling and cardiac hypertrophy induced by the chronic inhibition of nitric oxide synthesis. In addition, chronic inhibition of nitric oxide synthesis caused scattered lesions of myocardial fibrosis, which was significantly attenuated by cotreatment with hydralazine. These results suggest that long-term blockade of nitric oxide synthesis caused coronary microvascular remodeling and cardiac hypertrophy in rats in vivo by a mechanism other than arterial hypertension. In contrast, arterial hypertension contributed to the development of myocardial fibrosis induced by long-term blockade of nitric oxide synthesis.
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PMID:Chronic inhibition of nitric oxide synthesis causes coronary microvascular remodeling in rats. 749 Jan 55

We studied the effects of seven day treatment with the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine (L-NAME), administered in the drinking water (100 micrograms/ml ad lib) of female guinea pigs. The effects of NOS inhibition were evaluated in naive animals and in guinea pigs with ileitis induced by intraluminal trinitrobenzenesulfonic acid (TNBS). After 7 days, animals were anesthetized, a sterile saline lavage injected into an ileal loop and removed after 30 min for analysis. In naive guinea pigs, L-NAME caused a marked increase in ileal myeloperoxidase activity and conversion of the mucosa from an absorptive to a secretory state. TNBS-treated guinea pigs has a similar, marked increase in granulocyte infiltration and a mucosal secretory response. However, in contrast to naive animals, L-NAME treatment was anti-inflammatory, reverting all responses to the basal state. We conclude that intestinal nitric oxide serves an anti-inflammatory role under basal conditions, whereas in the TNBS model of chronic ileitis, nitric oxide is a critical mediator of gut injury.
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PMID:Nitric oxide: the Jekyll and Hyde of gut inflammation. 750 3

It has been suggested that chronic hypoxic pulmonary hypertension results from chronic hypoxic inhibition of endothelium-derived relaxing factor (EDRF) synthesis. We tested this hypothesis by studying whether chronic EDRF inhibition by N omega-nitro-L-arginine methyl ester (L-NAME) would induce pulmonary hypertension similar to that found in chronic hypoxia. L-NAME (1.85 mM) was given for 3 wk in drinking water to rats living in normoxia or hypoxia. Unlike chronic hypoxia, chronic L-NAME treatment did not increase pulmonary arterial pressure. Cardiac output was reduced and mean systemic arterial pressure was increased by chronic L-NAME treatment. The vascular pressure-flow relationship in isolated lungs was shifted toward higher pressures by chronic hypoxia and, to a lesser degree, by L-NAME intake. In isolated lungs, vasoconstriction in response to angiotensin II and acute hypoxia and vasodilation in response to sodium nitroprusside were increased by chronic L-NAME treatment in normoxia and chronic hypoxia. Chronic hypoxia, but not L-NAME, induced hypertensive pulmonary vascular remodeling. Chronic supplementation with the EDRF precursor L-arginine did not have any significant effect on chronic hypoxic pulmonary hypertension. We conclude that the chronic EDRF deficiency state, induced by L-NAME, does not mimic chronic hypoxic pulmonary hypertension in our model. In addition, EDRF proved to be less important for basal tone regulation in the pulmonary than in the systemic circulation.
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PMID:Chronic EDRF inhibition and hypoxia: effects on pulmonary circulation and systemic blood pressure. 750 6

The chronic inhibition of NO-synthase by NG-nitro-L-arginine methyl ester (L-NAME, a L-arginine analogue) induces a dose-dependent decrease in aortic cGMP and an increase in blood pressure. We used this pharmacological approach to evaluate the release of NO in vivo in spontaneously hypertensive rats (SHR); 15 SHR and 10 Wistar-Kyoto rats (WKY) were given 25 mg L-NAME/kg/d by gavage for 15 days; 10 SHR and 10 WKY rats given water for the same period were used as control. During the trial, 10/15 SHR given L-NAME died. Systolic blood pressure (mmHg) increased from 132 +/- 6 to 170 +/- 4 in WKY given L-NAME and from 169 +/- 4 to 242 +/- 6 in SHR given L-NAME. Aortic cGMP content (fmol/mg protein) was 2,204 +/- 382 and 2,076 +/- 461 fmol/mg control WKY and SHR (NS), and was decreased to 324 +/- 44 and 641 +/- 70 in WKY and SHR given L-NAME respectively (p < 0.0001 each). L-NAME increased plasma atrial natriuretic factor only in SHR. In summary, basal aortic cGMP content, reflecting the basal release of NO, was similar in WKY and SHR. The decrease in aortic cGMP content of SHR given L-NAME, due to the blockade of NO-synthase, was accompanied by a large increase in systolic blood pressure and a tremendous mortality rate. Thus, basal release of NO is probably not impaired in SHR, but represents a major counterregulatory mechanism in this genetic model of arterial hypertension.
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PMID:[Vasodilator effect of nitric oxide is a necessary counter-regulation in the spontaneously hypertensive rat]. 751 Apr 67


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