Influence Of Nitric Oxide Synthase Inhibitor Research Articles

Interplay between nitric oxide and vasoactive intestinal polypeptide in the pig gastric fundus smooth muscle

The aim of this study was to investigate the exact mechanism of interaction between nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) as inhibitory non-adrenergic non-cholinergic (NANC) neurotransmitters in isolated smooth muscle cells and smooth muscle strips of the pig gastric fundus. In isolated smooth muscle cells, the maximal relaxant effect of VIP (10 −9 M) was inhibited by 94% by the NO synthase (NOS) inhibitor N G-nitro- l-arginine ( l-NA, 10 −4 M) and by 85% by the inducible NOS (iNOS)-selective inhibitor N-(3-(aminomethyl)-benzyl)acetamide (1400W; 10 −6 M). The relaxant effect of VIP was reduced by more than 70% by the guanylyl cyclase inhibitor 1 H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ; 10 −6 M), the glucocorticoid dexamethasone (10 −5 M) and three protein kinase A inhibitors: ( R)- p-cyclic adenosine-3′,5′-monophosphothioate (( R)- p-cAMPS; 10 −6 M), {(8 R,9 S,11 S)-(−)-9-hydroxy-9- n-hexylester-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1 H,8 H,11 H-2,7 b,11 a-triazadibenzo[ a, g]cycloocta[ cde]-trin-den-1-one} (KT5720; 10 −6 M) and N-(2-( p-bromo-cinnamylamino)ethyl))-5-isoquinoline sulfonamide dihydrochloride (H-89; 10 −5 M). In contrast, no influence of the NOS inhibitors, ODQ, dexamethasone, nor the protein kinase A inhibitors could be observed on the relaxant effect of VIP in smooth muscle strips. These data demonstrate that the experimental method completely changes the influence of NOS inhibitors on the relaxant effect of VIP in the pig gastric fundus. The isolation procedure of the smooth muscle cells might induce iNOS that can be activated by VIP.

Peroxynitrite is not a major mediator of endothelial cell injury by activated neutrophils in vitro.

Human polymorphonuclear leukocytes (PMN) produce nitric oxide (NO), superoxide (O2.-) and peroxynitrite (ONOO-) upon stimulation. We investigated the role of ONOO- in PMN-induced injury to cultured bovine aortic endothelial cells (BAEC). BAEC were cocultured with phorbol 12-myristate 13-acetate (PMA)-activated human PMN (effector-to-target ratio, 10:1) and injury to BAEC was evaluated at intervals by 51Cr release assay. The levels of NO, O2.-, ONOO- and nitrotyrosine, a reaction product of ONOO-, were also measured, and the influence of NO synthase inhibitors, O2.- and hydroxyl radical scavengers and other effectors was examined. In BAEC cocultured with PMA-activated PMN, 51Cr release was significantly increased [14.6 +/- 2.2% at 2 h (p < 0.05) and 42.6 +/- 2.7% at 4 h (p < 0.01); control (nonactivated PMN), < 4%]. Superoxide dismutase (100 U/ml) reduced 51Cr release to 4.6 +/- 2.2% at 2 h (p < 0.05). N-Iminoethyl-L-ornithine (L-NIO, 0.1 mM) potentiated 51Cr release (30.6 +/- 3.8% at 2 h, p < 0.01), and the potentiation was eliminated by anti-CD18 monoclonal antibody. The 51Cr release was completely prevented by dimethyl sulfoxide or by deferoxamine. Treatment of PMN with L-NIO inhibited NO generation and increased O2.- production. The nitrotyrosine level did not increase in BAEC cocultured with PMA-activated PMN. NO-derived ONOO- is not a major cytotoxic mediator in BAEC injury by activated PMN. NO may have a cytoprotective effect by inhibiting PMN adherence to endothelial cells.

Nitric oxide synthesis inhibition attenuates morphine-induced place preference

Nitric oxide (NO) has been implicated in the actions of opioids. The aim of the present study was to investigate the role of NO in the mechanisms mediating the rewarding effects of morphine. Therefore, the influence of NO synthase inhibitor l-N- nitroarginine ( l-NOARG) on morphine-induced place preference in rats was studied. l-NOARG, when given at 20 mg/kg, IP, significantly inhibited the effect of morphine. l-NOARG by itself, when administered at 5 or 20 mg/kg, IP, appeared to have no reliable effect on place conditioning. The results suggest a possible role of NO in the opioid reward process.