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 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.
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PMID:Studies on the antinociceptive effects of sodium nitroprusside and molsidomine in mice. 956 42

We investigated whether a complete inhibition of nitric oxide (NO) formation caused by bacterial endotoxin (lipopolysaccharide, LPS) in vivo prevents the hypotension and restores the vascular hyporeactivity to normal in vivo and ex vivo. The combination of dexamethasone (Dex; 3 mg/kg at 30 min before LPS) plus aminoguanidine (AG; 15 mg/kg at 2 h after LPS) inhibited the overproduction of nitrate (an indicator of NO) in the plasma and aortic smooth muscle and also prevented the development of the delayed hypotension in rats treated with LPS for 6 h. However, the vascular hyporeactivity to norepinephrine (NE) was only partially improved either in vivo or ex vivo in endotoxemic rats treated with Dex plus AG. Pretreatment of aortic rings with Nomega-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2, 4]oxidazolo[4,3-a]quinoxalin-1-one (ODQ) enhanced the contraction to NE in rings obtained from LPS-treated rats, but not in those from Dex plus AG-treated endotoxemic rats. Methylene blue, an inhibitor of soluble guanylyl cyclase (GC), completely restored contractions to NE and aortic cGMP levels to normal either in LPS-treated rats or in Dex plus AG-treated endotoxemic rats, whereas the cGMP level was partially inhibited by ODQ in LPS-treated rats only. These results suggest that non-NO mediator(s) also activates soluble GC during endotoxemia. Interestingly, we found that in the presence of tetraethylammonium (an inhibitor of K+ channels) plus L-NAME or charybdotoxin [a specific inhibitor of large-conductance Ca2+-activated K+ (KCa) channels] plus ODQ, the vascular hyporeactivity to NE in the LPS-treated group was also completely restored to normal. In addition, in the presence of L-NAME or ODQ, the vascular hyporeactivity to high K+ was abolished in rings from the LPS-treated group. These results suggest that LPS causes the production of other mediator(s), in addition to NO, which also stimulates soluble GC (i.e., increases the formation of cGMP) and then activates the large-conductance KCa channels in the vascular smooth muscle causing vascular hyporeactivity.
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PMID:Nitric oxide-independent activation of soluble guanylyl cyclase contributes to endotoxin shock in rats. 974 61

To clarify further the role of cyclic GMP in mediating the relaxant response in guinea-pig trachea induced by sodium nitroprusside (SNP), the effects of soluble guanylyl cyclase inhibitors, methylene blue and 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ) on SNP-induced muscle relaxation and cyclic GMP accumulation were determined. SNP (0.3-100 microM) evoked a concentration-dependent relaxation of guinea-pig isolated tracheas precontracted with 0.3 microM carbachol. Preincubation of the preparations with methylene blue (10, 30 and 100 microM) resulted in a slight but concentration-dependent prevention of the relaxant response to SNP. In contrast, the relaxation to SNP was extensively prevented by 3 microM ODQ and almost abolished by 10 microM ODQ. SNP (30 microM) induced a significant elevation of cyclic GMP accumulation (from 1.34+/-0.14 to 5.39+/-0.28 pmol mg(-1) protein, n= 5; P<0.001), which was partially attenuated by 100 microM methylene blue (3.11+/-0.51 pmol mg(-1) protein, n=5; P<0.05), whereas completely abolished by 10 microM ODQ (1.31+/-0.28 pmol mg(-1) protein, n = 5; P<0.001). Methylene blue, but not ODQ and Nomega-nitro-L-arginine methyl ester (L-NAME), caused a concentration-dependent contraction in the tracheal preparation. The tension produced by 100 microM methylene blue was 41.8+/-4.3% (0.3 microM carbachol as 100%; n = 12). Moreover, the non-selective muscarinic receptor antagonist atropine and the M3-selective antagonist 4-diphenylacetoxy-N-methylpiperidine methiodine greatly inhibited the contractile effect evoked by methylene blue (100 microM). In conclusion, this study provides substantial evidence that SNP-induced muscle relaxation in guinea-pig trachea is completely via a cyclic GMP-dependent mechanism. Furthermore, ODQ, but not methylene blue, will likely become an important tool in differentiating between cyclic GMP-dependent and -independent effects of nitric oxide.
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PMID:Comparison of two soluble guanylyl cyclase inhibitors, methylene blue and ODQ, on sodium nitroprusside-induced relaxation in guinea-pig trachea. 986 42

The purpose of this study was to examine the role of the nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) system in the regulation of the ductus arteriosus (DA) patency in fetal rats. Pregnant rats were administered N(G)-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg, ip), an NO synthase (NOS) inhibitor; methylene blue (30, 50 and 100 mg/kg, ip), a soluble guanylate cyclase inhibitor; or indomethacin (3 mg/kg, po), a cyclooxygenase inhibitor, at various times before cesarean section. Dams were decapitated to obtain the fetuses by cesarean section, and fetuses were rapidly frozen in an acetone-dry ice mixture. Using rapid freezing and shaving methods, the calibers of the DA, pulmonary artery (PA) and descending aorta (Ao) were measured to evaluate the effects of treatment. L-NAME reduced the DA calibers to 86% of the initial values, but recovery to the control levels occurred 6 hr after the injection. Indomethacin decreased the DA calibers to 34% of the control values and sustained the DA constriction until 24 hr after the treatment. Methylene blue caused DA constriction to almost the same degree as indomethacin, but the levels normalized within 24 hr after the treatment. We conclude that L-NAME caused a slight constriction of the DA, whereas methylene blue and indomethacin caused marked constriction of the vessels, suggesting that the NO-cGMP system as well as prostaglandins contribute to the DA patency.
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PMID:Role of the nitric oxide-cGMP system in the regulation of ductus arteriosus patency in fetal rats. 1065 Oct 46

The purpose of this study was to investigate the role of the L-arginine/nitric oxide (NO)/cGMP pathway in p-benzoquinone-induced writhing model in mouse. L-arginine, a NO precursor, displayed antinociceptive effects at the doses of 0.125-1.0 mg/kg. When the doses of L-arginine were increased gradually to 10-100 mg/kg, a dose-dependent triphasic pattern of nociception-antinociception-nociception was obtained. The NO synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) (18.7515 mg/kg), possessed antinociceptive activity. Methylene blue (MB), a guanylyl cyclase and/or NOS inhibitor, (5-160 mg/kg) also produced a dose-dependent triphasic response. When L-arginine (50 mg/ kg) was combined with L-NAME (75 mg/kg). L-arginine-induced antinociception did not change significantly. Cotreatment of L-arginine with 5 mg/kg MB significantly decreased MB-induced antinociception and reversed the nociception induced by 40 mg/kg MB to antinociception. It is concluded that the components of L-arginine/nitric oxide/cGMP cascade may participate in nociceptive processes both peripherally and centrally by a direct effect on nociceptors or by the involvement of other related pathways of nociceptive processes induced by NO.
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PMID:Participation of the components of L-arginine/nitric oxide/cGMP cascade by chemically-induced abdominal constriction in the mouse. 1095 47

We studied the combined effects of indomethacin, a cyclooxygenase inhibitor, and N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, on the patency of the ductus arteriosus (DA) in fetal rats. Pregnant rats were administered indomethacin (3 mg/kg) orally 3 h before cesarean section, and then L-NAME (5 and 50 mg/kg), D-NAME, an enantiomer of L-NAME (50 mg/kg), or methylene blue, a soluble guanylate cyclase inhibitor (100 mg/kg), was injected intraperitoneally at various times before the cesarean section. Using rapid freezing and shaving methods, the calibers of the DA were measured. Compared with the indomethacin alone group, L-NAME caused a rapid and marked increase in the DA caliber 0.5 h after injection in fetal rats in which the DA was constricted by treatment with indomethacin. Subsequently, the transient ductal dilatation was completely reversed by 3 h after the L-NAME injection. Methylene blue also caused a biphasic response, but D-NAME did not affect the DA caliber. We conclude that the inhibition of both cyclooxygenase (indomethacin) and NO synthase (L-NAME) or NO action (methylene blue) causes a biphasic effect on the DA caliber in fetal rats.
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PMID:Biphasic response of the ductus arteriosus to combined administration of indomethacin and L-NAME in fetal rats. 1109 10

This study investigated the hypothesis that atrial natriuretic peptide (ANP) responses are mediated by particulate guanylate cyclase in the pulmonary vascular bed of the cat. When tone in the pulmonary vascular bed was raised to a high steady level with the thromboxane mimic U-46619, injections of ANP caused dose-related decreases in lobar arterial pressure. After administration of HS-142-1, an ANP-A- and ANP-B-receptor antagonist, vasodilator responses to ANP were reduced. The nitric oxide (NO) synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) enhanced ANP vasodilator responses, suggesting that inhibition of NO modulates ANP responses. L-NAME administration with constant 8-bromo-cGMP infusion attenuated the increased vasodilator response to ANP, suggesting that supersensitivity to ANP occurs upstream to activation of a cGMP-dependent protein kinase. In pulmonary arterial rings, ANP produced concentration-related vasorelaxant responses with and without endothelium. Methylene blue, L-NAME, or N(omega)-monomethyl-L-arginine did not alter ANP vasorelaxant responses. These data show that ANP supersensitivity observed in the intact pulmonary vascular bed is not seen in isolated pulmonary arterial segments, suggesting that it may only occur in resistance vessel elements. These results suggest that ANP responses occur through activation of ANP-A and/or -B receptors in an endothelium-independent manner and are modulated by NO in resistance vessel elements in the pulmonary vascular bed of the cat.
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PMID:L-NAME enhances responses to atrial natriuretic peptide in the pulmonary vascular bed of the cat. 1135 72

In isolated coronary arteries, hypoxia induces an increase in tone by releasing an unidentified endothelium-derived contracting factor (EDCF). Isometric force was measured in an isolated rabbit coronary artery ring at 37 degrees C in control and high K+ (40 mM) pre-contracted conditions. Hypoxia (15 mmHg pO2) induced by equilibrating the perfusate with nitrogen. Hypoxia did not affect the resting tone but induced an endothelium-dependent contraction on pre-contracted rings. Inhibitors of nitric oxide (NO) were tested, L-NAME (10(-4) M) totally and L-NMMA (10(-4) M) partially convert the hypoxic contraction to an hypoxic relaxation. The addition of L-arginine (10(-4) or 10(-3) M) did not restore the response. Methylene blue (10( -5) M) and ODQ (1 H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one, 10(-5) M), both inhibitors of guanylate cyclase, also changed the hypoxic contraction into a hypoxic relaxation. Catalase (1200 U/ml), which decomposes hydrogen peroxide (H2O2), and superoxide dismutase (150 U/ml, SOD), a free radical scavenger, did not change the hypoxic response but quinacrine (50 microM), an inhibitor of phospholipase A2, significantly decreased it. Inhibitors of arachidonic acid metabolism (indomethacin, diethylcarbamazine, miconazole) however did not affect the hypoxic response. We conclude that in K+ pre-contracted rabbit coronary artery rings, hypoxia induces a contraction which is nitric oxide and arachidonic acid dependent.
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PMID:Possible role of nitric oxide and arachidonic acid pathways in hypoxia-induced contraction of rabbit coronary artery rings. 1147 Oct 68

The influence of nitric oxide (NO) on antinociceptive activity of diazepam (DZ), chlordiazepoxide (CDP) and clonazepam (CZ) was examined using the writhing test in mice. The effect of DZ was also studied in mice using hot plate and tail flick tests. DZ (1.25, 2.5 and 5 mg/kg), CDP (1.25, 2.5, 5, 10 and 20 mg/kg) and CZ (0.075, 0.3125, 0.625, 1.25 and 2.5 mg/kg) produced significant, dose-dependent (DZ, CDP) antinociception in mice. The benzodiazepines (BZs)-induced antinociception was antagonized by flumazenil (5 mg/kg) and was not changed by naloxone (2.5, 5 and 10 mg/kg), except that of CZ, which was reversed by 5 mg/kg of naloxone. NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) as well as 7-nitroindazole (7-NI) intensified antinociceptive activity of BZs. The antinociceptive effect resulting from co-administration of L-NAME with CZ and 7-NI with CDP was reversed by L-arginine. Methylene blue (MB) increased, whereas L-arginine (but not D-arginine) decreased antinociceptive effects of the studied BZs. These results suggest that the NO-cGMP pathway is involved in the mechanism of BZs-induced antinociception in the writhing test in mice.
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PMID:Role of nitric oxide in benzodiazepines-induced antinociception in mice. 1202 41

The influence of nitric oxide (NO) on anticonvulsant activity of diazepam and clonazepam was examined in the pentetrazole- and electroshock-induced seizure models in mice. Protective efficacy of the threshold dose of diazepam against pentetrazole-induced clonic and tonic seizures, and death was significantly increased by NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) while 7-nitroindazole (7-NI) was slightly less effective. The above intensifying effect of L-NAME on antiepileptic activity of diazepam was reversed by L-arginine, a substrate for NO formation, but not by D-arginine. Methylene blue, the guanylate cyclase inhibitor, increased the protective efficacy of diazepam and clonazepam in the pentetrazole-induced seizures. 7-NI was able to potentiate the protective efficacy of diazepam and clonazepam in electroshock-induced tonic hindlimb extension. These findings suggest that the cGMP/NO system may participate in antiepileptic effects of benzodiazepines.
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PMID:Role of nitric oxide in anticonvulsant effects of benzodiazepines in mice. 1292 45


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