Disease relevance of NSC 72843

• The possible modulatory role of nitric oxide (NO) in neurogenic edema formation in rat paw skin, induced by electrical stimulation of the saphenous nerve, was investigated by using two NO synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI) [1].
• Pre-injury treatment with 7-nitroindazole, which probably inhibits this immediate increase in NO by neuronal NOS, is effective in improving neurological outcome in some models of traumatic brain injury (TBI) [2].
• Furthermore, we show that inhibition of neuronal nitric-oxide synthase (nNOS) by 7-nitroindazole is sufficient to prevent retinal degeneration implicating a key role for neuronal nitric oxide (NO) in this model [3].
• The selective inhibitor of neuronal nitric oxide synthase, 7-nitroindazole, reduces the delayed neuronal damage due to forebrain ischemia in rats [4].
• 7-Nitroindazole inhibits pial arteriolar vasodilation in a rat model of pneumococcal meningitis [5].

Psychiatry related information on NSC 72843

• At antidystonic effective doses neither L-NNA nor L-NAME caused observable side effects, whereas 7-nitroindazole exerted moderate reduction of locomotor activity [6].

High impact information on NSC 72843

• 45Ca uptake by cardiac SR vesicles, catalyzed by Ca2+-ATPase, was inhibited by NO. produced endogenously from cardiac SR NOS, and 7-nitroindazole, a selective nNOS inhibitor, completely prevented this inhibition [7].
• Cell death after oxygen and glucose deprivation was ameliorated in male cultures, but not female cultures, by the addition of 7-nitroindazole, a neuronal nitric oxide synthase inhibitor [8].
• When spatial learning was inhibited by treatment with 7-nitroindazole, an inhibitor of brain nitric oxide synthase, the increase in the hippocampal BDNF mRNA did not occur [9].
• In contrast, neuronal NOS (NOS1)-deficient mice and wild-type mice treated with the nonspecific NOS inhibitor NG-nitro-L-arginine methyl ester and the NOS1-specific inhibitor 7-nitroindazole all had delayed parasite clearance [10].
• Cerebral blood flow response as well as BOLD signal intensity changes following electrical stimulation were abolished within 10 min after application of 7 nitroindazole, whereas somatosensory-evoked potentials were only slightly affected but still clearly detectable [11].

Chemical compound and disease context of NSC 72843

• Administration (i.c.v.) of N-nitro-L-arginine methyl ester, but not 7-nitroindazole, 30 minutes prior to lethal 10-minute ischemia, significantly abolished the acquired tolerance [12].
• Systemic ONO-1714 at 1-10 mg/kg suppressed carrageenan-induced thermal hyperalgesia in rats, an effect being equivalent to the antinociception caused by L-NAME or 7-nitroindazole at 25 mg/kg [13].
• These results may involve motor effects of this compounds, since inhibitors of NOS, NG-nitro-L-arginine (L-NOARG), N(G)-nitro-L-arginine methylester (L-NAME), N(G)-monomethyl-L-arginine (L-NMMA), and 7-Nitroindazole (7-NIO), induced catalepsy in mice [14].
• Additional groups of rats received NG-nitro-L-arginine and NG-monomethyl-L-arginin, non-selective NO synthase inhibitors, 7-nitroindazole, a neuronal NOS inhibitor, and aminoguanidine and L-N6-(1-iminoethyl) lysine, inducible NO synthase (iNOS) inhibitors before preconditioning, and were subjected to 60 min of ischemia [15].
• NMDA-mediated toxicity to striatal neurons is not reversed by 7-nitroindazole, an inhibitor of neuronal nitric oxide synthase [16].

Biological context of NSC 72843

• Neither SMT (at both doses) nor 7-nitroindazole influenced the increase in brain water content, intracranial pressure, and CSF white blood cell counts in pneumococci-challenged rats [5].
• Cerebral blood flow (CBF), cerebral blood volume (CBV), and blood oxygenation level dependent (BOLD) responses to electrical stimulation of the forepaw were measured before and after an intraperitoneal bolus of 7-nitroindazole (7-NI), an in vivo inhibitor of the neuronal isoform of nitric oxide synthase [17].
• Pretreatment of a separate group of rats with 7-nitroindazole (20 mg/kg intraperitoneally), a relatively selective inhibitor of neuronal NO synthase, abolished the increase in velocity at hematocrits greater than 20%, but the maximum velocity attained at the lowest hematocrit was similar to that in the control group [18].
• 7-Nitroindazole, a selective inhibitor of neuronal NOS, did not elevate blood pressure [19].
• Pretreatment with N-methyl-D-aspartate receptor antagonist MK-801 fully abolished the effects of 7-nitroindazole on neurogenesis and cyclic AMP response element binding protein phosphorylation [20].

Anatomical context of NSC 72843

• We examined whether 7-nitroindazole (7-NI), a putative inhibitor of neuronal nitric oxide synthase (nNOS), decreases cerebral infarction 24 h after proximal middle cerebral artery (MCA) occlusion [21].
• 7-Nitroindazole impedes erythrocyte flow response to isovolemic hemodilution in the cerebral capillary circulation [18].
• In a separate experiment administration of 7-nitroindazole for 48 h after MPP+ injections significantly attenuated substantia nigra degeneration in rats [22].
• These results indicate that the inhibition of neuronal nitric oxide synthase by 7-nitroindazole protects neurons from seizure-induced toxicity despite reducing blood flow and oxygen supply to the hippocampus [23].
• Here we show that 5-bromodeoxyuridine-labeled dividing progenitor cells in the dentate gyrus were significantly increased in mice receiving 7-nitroindazole, a selective neuronal nitric oxide synthase inhibitor, and in null mutant mice lacking neuronal nitric oxide synthase gene (nNOS-/-) 6 h and 4 weeks after 5-bromodeoxyuridine incorporation [20].

Associations of NSC 72843 with other chemical compounds

• We examined the effects of N omega-nitro-L-arginine methyl ester (L-NAME), a general inhibitor of nitric oxide synthase (NOS), and 7-nitroindazole (7-NI), a selective inhibitor of neuronal NOS, on aprikalim-induced cerebral vasodilation [24].
• Inhibition of monoamine oxidase contributes to the protective effect of 7-nitroindazole against MPTP neurotoxicity [25].
• After administration of the vehicle for 7-nitroindazole (peanut oil), L-arginine (100 micromol/kg per min for 10 min) decreased both resting and baroreceptor-unloaded RSNA, whereas after pretreatment with 7-nitroindazole, the L-arginine-induced suppression was reversed, in Dahl salt-sensitive rats receiving a high-salt diet [26].
• Alone, NOS inhibitors and promoters do not affect prepulse inhibition; however, when tested in combination with PCP, the NOS inhibitors, L-NOARG, 7-nitroindazole and arcaine--but not the NR2B-selective polyamine site NMDA antagonist, eliprodil--attenuated PCP-induced disruption of prepulse inhibition of the acoustic startle response [27].
• The selective neuronal NOS inhibitor, 7-nitroindazole (7-NI; 100 micromol/l) increased EFS-induced contraction only in segments from ouabain-treated rats [28].

Gene context of NSC 72843

• Treatment of cirrhotic rats for 7 days with the specific nNOS inhibitor 7-nitroindazole (7-NI) normalized the low SVR and mean arterial pressure, elevated cardiac index, and reversed the positive sodium balance [29].
• 7-nitroindazole, a bNOS-selective inhibitor, protects in central nervous system injury [30].
• We found that intrathecal administration of 7-nitroindazole (a selective neuronal NOS inhibitor), but not L-N(5)-(1-iminoethyl)-ornithine (a selective endothelial NOS inhibitor), significantly reduced carrageenan-induced thermal hyperalgesia in both the early phase and the late phase in iNOS knockout mice [31].
• Intradermal injections of L-NAME (100 nmol site(-1)), another NOS inhibitor 7-nitroindazole (10 nmol site(-1)) and the NO scavenger haemoglobin (0.01-10 nmol site(-1)) also inhibited SP-induced scratching [32].
• Isoflurane-induced changes in MAP were monitored in rats following pretreatment with vehicle or one of the following NOS inhibitors: L-NG)monomethyl-L-arginine (L-NMMA), which is non-selective; L-NG)nitro arginine (L-NOARG), which is more selective for nNOS and eNOS; and 7-nitroindazole (7-NI), which is selective for nNOS [33].

Analytical, diagnostic and therapeutic context of NSC 72843

• 7-Nitroindazole produced a significant attenuation of the activation-elicited CBF (P<10(-6)), CBV (P<10(-6)), and BOLD responses (P<10(-6)), without affecting the baseline perfusion level [17].
• The specific inhibitor of neuronal NOS, 7-nitroindazole (7-NI), given at reperfusion, showed no protection, although preischemic treatment with 7-NI decreased infarct volume by 40% [34].
• Furthermore, intrathecal injection of either L-NAME or 7-nitroindazole, a selective nNOS inhibitor, markedly attenuated mechanical pain hypersensitivity at both 2 and 24h after CFA injection [35].
• The present study was performed to assess the prophylactic effect of 7-nitroindazole (7-NI), an inhibitor of neuronal nitric oxide synthase (nNOS), in an animal model of heatstroke [36].
• OBJECTIVE: To test the hypothesis that microinjection into the MeA of two NO synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME) or 7-nitroindazole (7-NI), would produce anxiolytic effects [37].

References