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)

Effect of treatment with p-bromo-methamphetamine (V-111), the serotonin depleting drug, on two way avoidance conditioning (CAR) was studied in raphe lesioned male Wistar rats. Both sham lesioned and raphe lesioned animals treated with V-111 showed increased avoidance acquisition and increased number of inter-trial responses. Lesions of the raphe nuclei increased by itself the number of avoidance responses, the treatment with V-111 however produced further facilitation of avoidance acquisition. These results are discussed in terms of the role oserotonergic system in the processes of learning and retention of CAR, and direct action of V-111 on serotonergic system of the brain is suggested.
Pol J Pharmacol Pharm
PMID:Effects of p-bromo-methamphetamine (V-111) on conditioned avoidance behavior in rats with lesioned raphe nuclei. 50 68

Endothelium-dependent relaxations to bradykinin (BK) in U46619-contracted, indomethacin (INDO)-treated porcine coronary artery (PCA) rings are modestly attenuated by the nitric oxide (NO) synthase inhibitor, N omega-nitro-l-arginine methyl ester (L-NAME); whereas, when contracted with KCl, L-NAME abolishes BK relaxations. In contrast, endothelium-dependent arachidonic acid (AA) relaxations of U46619-contracted, INDO-treated PCA rings are not affected by L-NAME. AA does not relax KCl-contracted rings. Since BK is known to release AA, we postulated that the non-NO component of BK relaxation of the PCA is mediated by AA or an AA metabolite. Changes in tension of PCA rings to BK and AA were determined in the presence and absence of phospholipase (PLA), cyclooxygenase (CO), lipoxygenase (LO) and cytochrome P-450 (cP450) inhibitors. Responses to BK were attenuated by PLA inhibitors. No other inhibitors, however, eliminated responses to either BK or AA. The results suggest that relaxation to BK in PCA rings requires PLA activity, but relaxation to AA is independent of PLA, CO, LO or cP450 activity. We conclude that relaxation to BK and AA in the PCA is mediated by a product of an unidentified pathway of AA metabolism or by an unknown second messenger system resident within the endothelium and responsive to AA.
Pol J Pharmacol
PMID:Endothelium-dependent relaxation to arachidonic acid in porcine coronary artery: is there a fourth pathway? 762 May 17

Endogenous nitric oxide (NO) opposes the vasoconstriction that occurs when lungs are ventilated with a hypoxic gas mixture. However, the contribution of NO to pulmonary vascular resistance when alveolar gas tension is not reduced remains to be defined. Here, we investigated the hypothesis that endogenous NO is a determinant of pulmonary vascular resistance in isolated perfused rabbit lungs ventilated with a normoxic gas mixture. Moreover, we wished to establish that, as flow rate increases, the contribution of NO to vascular resistance increases. In addition, we examined the contribution of NO to the longitudinal distribution of pulmonary vascular resistance. Pressure-flow curves were generated in isolated blood perfused rabbit lungs by varying flow rate from 50 ml/min to 300 ml/min in the presence and absence of the cyclooxygenase inhibitor, indomethacin (100 microM) and the inhibitor of NO synthesis, NG-nitro-L-arginine methyl ester (L-NAME, 100 microM). Indomethacin did not alter total pulmonary vascular resistance or the longitudinal distribution of resistance. In contrast, L-NAME administration resulted in significant, flow-related increases in total vascular resistance, i.e., after L-NAME, as flow rate increased, the increment in resistance increased. L-NAME-induced increases in total pulmonary vascular resistance were the result of flow-related increases in the arterial component of vascular resistance. These results provide support for the hypothesis that NO is an important determinant of pulmonary vascular resistance in the rabbit and that the major site of NO activity resides in the arterial side of that circulation.
Pol J Pharmacol
PMID:Inhibition of nitric oxide synthesis results in a selective increase in arterial resistance in rabbit lungs. 762 May 18

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.
Pol J Pharmacol
PMID:Inhibition of nitric oxide synthesis improves arterial oxygenation in ethchlorvynol-induced acute lung injury in dogs. 886 43

Recent studies suggested that the L-arginine/nitric oxide (NO)/cyclic GMP pathway is involved in the modulation of pain perception. The present experiments were undertaken to find out the role of this pathway in the antinociception induced by oxotremorine administration. Male mice of the CD-1 strain were injected with different doses of the muscarinic agonist oxotremorine (0.005, 0.01, 0.02, 0.03 mg/kg i.p.) 5 min after the administration of saline solution or the inhibitors of NO synthase NG-nitro-L-arginine methyl ester (L-NAME: 10 and 20 mg/kg, i.p.) or NG-nitro-L-arginine (N-ARG: 10 and 20 mg/kg i.p.). Oxotremorine induced a dose- and time-dependent analgesic effect in mice, which was significantly increased by L-NAME and N-ARG administration. Either doses of the NO inhibitors given alone had no effect on the nociceptive threshold. The present results show a role of NO in the antinociception mediated by the muscarinic receptor stimulation and suggest that it exerts an inhibitory action on cholinergic analgesia.
Pol J Pharmacol
PMID:Nitric oxide synthase inhibitors enhance the antinociceptive effects of oxotremorine in mice. 943 49

The effects of the NO donor molsidomine and the inhibitors of the NO synthase (NOS) 7-nitroindazole (7-NI) and NG-nitro-L-arginine methyl ester (L-NAME) on the motor hyperactivity induced by indirect (amphetamine and cocaine) or direct (SKF 38393 and bromocriptine) dopamine (DA) agonists were studied in rats. The hyperactivity induced by 0.5 mg/kg of amphetamine or 5 mg/kg of cocaine was potentiated in a dose-dependent manner by molsidomine (30-100 mg/kg), but attenuated by 7-NI (3-30 mg/kg) or L-NAME (3-30 mg/kg). The NOS inhibitors also inhibited the locomotor hyperactivity evoked by 15 mg/kg of SKF 38393 (a DA D1 agonist) or 5 mg/kg of bromocriptine (a DA D2 agonist). On the other hand, the hyperactivity induced by those direct DA receptor agonists was potentiated by molsidomine. The present findings provide further evidence for an interaction at the behavioral level between NO and the DA-mediated effects of amphetamine and cocaine; moreover, they seem to indicate that both DA D1 and DA D2 receptor subtypes are under such influence.
Pol J Pharmacol
PMID:Nitric oxide (NO) pathway and locomotor hyperactivity towards dopaminomimetics in rats. 956 27

The present study examined effects of the two nitric oxide synthase (NOS) inhibitors, N-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI), as well as of the NO donor molsidomine on the anticonvulsant activity of conventional antiepileptic drugs (diphenylhydantoin and carbamazepine) and competitive (CGP 37,849) and non-competitive (dizocilpine) NMDA receptor antagonists against the maximal electroshock in mice. It was found that L-NAME (25 and 50 mg/kg) did not affect the anticonvulsant activity of either drug, having had no influence on their anticonvulsive ED50 values. 7-NI (50 and 100 mg/kg) reduced the anticonvulsive ED50 (augmentation of the anticonvulsant activity) of CGP 37,849 and dizocilpine, raised the anticonvulsive ED50 (attenuation of the anticonvulsant activity) of diphenylhydantoin and had no influence on the anticonvulsant effect of carbamazepine. At the same time, augmentation of the anticonvulsant activity (reduction of the ED50 values) of diphenylhydantoin, carbamazepine and CGP 37,849, but not of dizocilpine, was observed after molsidomine (100-150 mg/kg). Moreover, 7-NI (100 mg/kg) and molsidomine (100 and 150 mg/kg), but not L-NAME (25 and 50 mg/kg), raised the threshold for electroconvulsions. The obtained results indicate that alterations in the anticonvulsant activity of the investigated drugs evoked by 7-NI and mosidomine, may result from non-specific effects of the NOS inhibitor and the NO donor, having no connection with the brain NO pathway.
Pol J Pharmacol
PMID:Effect of nitric oxide synthase inhibitors and molsidomine on the anticonvulsant activity of some antiepileptic drugs. 956 37

The participation of nitric oxide (NO) in antinociceptive activity of molsidomine and sodium nitroprusside (SNP) was studied in mice using the writhing test. Molsidomine (300 and 150 mg/kg) and SNP (1.52-0.38 mg/kg) induced antinociception that was antagonized by naloxone. L-arginine (500-62.5 mg/kg) did not produce antinociceptive effects, whereas N omega-nitro-L-arginine methyl ester (L-NAME) (37.5-150 mg/kg) induced antinociception which was suppressed by naloxone. Methylene blue did not change the molsidomine- and SNP-induced antinociception, but significantly intensified that produced by L-NAME. L-arginine increased antinociceptive effect of molsidomine but not that of SNP. Antinociceptive activity of L-NAME was partially reversed by L-arginine. D-arginine failed to influence these effects. The present findings suggest that the NO-cGMP pathway is not involved in the mechanism of molsidomine- and SNP-induced antinociception in the writhing test in mice.
Pol J Pharmacol
PMID:Studies on the antinociceptive effects of sodium nitroprusside and molsidomine in mice. 956 42

The regulation of vascular wall homeostasis by nitric oxide (NO) generated by endothelium is being intensively studied. In the present paper, the involvement of NO in the vascular endothelial growth factor (VEGF), insulin or leptin-stimulated proliferation of human endothelial cells (HUVEC) was measured by [3H]thymidine or bromodeoxyuridine incorporation. VEGF and insulin, but not leptin, increased NO generation in HUVEC, as detected with ISO-NO electrode. Proliferation of HUVEC induced by leptin was not changed or was higher in the presence of N(omega)-nitro-L-arginine methyl ester (L-NAME) a nitric oxide synthase (NOS) inhibitor. In contrast, L-NAME blunted the proproliferative effect of VEGF and insulin. Furthermore, we demonstrated that, in human arterial smooth muscle cells (hASMC) transfected with endothelial NOS (eNOS) gene, the generation of biologically active VEGF protein was NO-dependent. Inhibition of NO generation by L-NAME decreased the synthesis of VEGF protein and attenuated HUVEC proliferation induced by conditioned media from transfected hASMC. Endothelium-derived NO seems to participate in VEGF and insulin, but not leptin, mitogenic activity. Additionally, the small amounts of NO released from endothelial cells, as mimicked by eNOS transfection into hASMC, may activate generation of VEGF in sub-endothelial smooth muscle cells, leading to increased synthesis of VEGF protein necessary for turnover and restitution of endothelial cells.
Acta Biochim Pol 1999
PMID:Nitric oxide mediates the mitogenic effects of insulin and vascular endothelial growth factor but not of leptin in endothelial cells. 1069 78

Our aim was to verify potency and selectiveness of two most widely used drugs regarded as NOS-2 inhibitors: L-N6-(1-iminoethyl)-lysine (L-NIL) and S-methylisothiourea sulphate (SMT). Thioglycolate-elicited rat peritoneal macrophages and coronary endothelium of isolated guinea pig heart were used as assay systems for NOS-2 and NOS-3, respectively. A non-selective NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) was used as a reference compound. We found that L-NIL but not SMT was a selective NOS-2 inhibitor. Interestingly, L-NAME displayed selectivity towards NOS-3.
Pol J Pharmacol
PMID:L-N6-(1-iminoethyl)-lysine (L-NIL) but not S-methylisothiourea sulphate (SMT) displays selectivity towards NOS-2. 1081 46


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