Exercise training with concomitant nitric oxide synthase inhibition improved anxiogenic behavior, spatial cognition, and BDNF/P70S6 kinase activation in 20-month-old rats

2018 ◽  
Vol 43 (1) ◽  
pp. 45-53 ◽  
Author(s):  
Mojtaba Salehpour ◽  
Fariba Khodagholi ◽  
Arman Zeinaddini Meymand ◽  
Maryam Nourshahi ◽  
Ghorbangol Ashabi
Keyword(s):  
Nitric Oxide ◽  
Prefrontal Cortex ◽  
Nitric Oxide Synthase ◽  
Low Dose ◽  
Caspase 3 ◽  
P70s6 Kinase ◽  
Protein Levels ◽  
Old Rats ◽  
Oxide Synthase

This study aimed to investigate the effect of exercise and nitric oxide synthase (NOS) inhibition on memory, anxiety, and protein levels of brain-derived neurotrophic factor (BDNF) and P70S6 kinase (P70S6K). Twenty-month-old rats were divided into 6 groups: a control group, 2 groups treated with l-nitro-arginine methyl ester (L-NAME) (25 or 100 mg/kg) for 63 days, 2 groups treated with L-NAME (25 or 100 mg/kg) for 63 days plus 2 months of exercise, and 1 group treated with exercise. Behavioral tests were conducted to determine the anxiolytic and memory-improving role of exercise and NOS inhibition. BDNF, P70S6K, and cleaved caspase-3 protein levels in the hippocampus and prefrontal cortex were evaluated by Western blotting. Exercise and L-NAME (25 mg/kg) or their combination had an anxiolytic effect and improved spatial memory in old rats compared with the control or exercised group, respectively. Exercise and treatment with a low dose of L-NAME (25 mg/kg) each increased BDNF and P70S6K in the hippocampus and prefrontal cortex compared with levels in control rats. In comparison with exercise alone, co-treatment with exercise and a low dose of L-NAME (25 mg/kg) also increased BDNF and P70S6K in the hippocampus. The neuronal level of cleaved caspase-3 was reduced in the L-NAME (25 mg/kg) + exercise group compared with the exercised group. The L-NAME (100 mg/kg) + exercise treatment had no positive behavioral or molecular effects compared with exercise alone. The protective role of NOS inhibition and aerobic exercise against aging is probably modulated via BDNF and P70S6K in the brain.

Geldanamycin inhibits hemorrhage-induced increases in caspase-3 activity: role of inducible nitric oxide synthase

2007 ◽  
Vol 103 (3) ◽  
pp. 1045-1055 ◽  
Author(s):  
Juliann G. Kiang ◽  
Phillip D. Bowman ◽  
Xinyue Lu ◽  
Yansong Li ◽  
Brian W. Wu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Caspase 3 ◽  
Gene Transfection ◽  
Organ Injury ◽  
Molecular Events ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Hemorrhage has been shown to increase inducible nitric oxide synthase (iNOS) and deplete ATP levels in tissues and geldanamycin limits both processes. Moreover, it is evident that inhibition of iNOS reduces caspase-3 and increases survival. Thus we sought to identify the molecular events responsible for the beneficial effect of geldanamycin. Hemorrhage in mice significantly increased caspase-3 activity and protein while treatment with geldanamycin significantly limited these increases. Similarly, geldanamycin inhibited increases in proteins forming the apoptosome (a complex of caspase-9, cytochrome c, and Apaf-1). Modulation of the expression of iNOS by iNOS gene transfection or siRNA treatment demonstrated that the level of iNOS correlates with caspase-3 activity. Our data indicate that geldanamycin limits caspase-3 expression and protects from organ injury by suppressing iNOS expression and apoptosome formation. Geldanamycin, therefore, may prove useful as an adjuvant in fluids used to treat patients suffering blood loss.

Vasculoprotective Role of Inducible Nitric Oxide Synthase at Inflammatory Coronary Lesions Induced by Chronic Treatment With Interleukin-1β in Pigs in Vivo

Circulation ◽  
1997 ◽  
Vol 96 (9) ◽  
pp. 3104-3111 ◽  
Author(s):  
Yoshihiro Fukumoto ◽  
Hiroaki Shimokawa ◽  
Toshiyuki Kozai ◽  
Toshiaki Kadokami ◽  
Kouichi Kuwata ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Chronic Treatment ◽  
Interleukin 1Β ◽  
Coronary Lesions ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Neuronal nitric oxide synthase and systemic vasodilation in rats with cirrhosis

2000 ◽  
Vol 279 (6) ◽  
pp. F1110-F1115 ◽  
Author(s):  
Lieming Xu ◽  
Ethan P. Carter ◽  
Mamiko Ohara ◽  
Pierre-Yves Martin ◽  
Boris Rogachev ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Liver Cirrhosis ◽  
Nitric Oxide Synthase ◽  
Control Treatment ◽  
Sodium Balance ◽  
Hyperdynamic Circulation ◽  
Molecular Approaches ◽  
Advanced Liver Cirrhosis ◽  
Oxide Synthase

Cirrhosis is typically associated with a hyperdynamic circulation consisting of low blood pressure, low systemic vascular resistance (SVR), and high cardiac output. We have recently reported that nonspecific inhibition of nitric oxide synthase (NOS) with nitro-l-arginine methyl ester reverses the hyperdynamic circulation in rats with advanced liver cirrhosis induced by carbon tetrachloride (CCl4). Although an important role for endothelial NOS (eNOS) is documented in cirrhosis, the role of neuronal NOS (nNOS) has not been investigated. The present study was carried out to specifically investigate the role of nNOS during liver cirrhosis. Specifically, physiological, biochemical, and molecular approaches were employed to evaluate the contribution of nNOS to the cirrhosis-related hyperdynamic circulation in CCl4-induced cirrhotic rats with ascites. Cirrhotic animals had a significant increase in water and sodium retention. In the aorta from cirrhotic animals, both nNOS protein expression and cGMP concentration were significantly elevated compared with control. 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. Increased plasma arginine vasopressin concentrations in the cirrhotic animals were also repressed with 7-NI in association with diminished water retention. The circulatory changes were associated with a reduction in aortic nNOS expression and cGMP. However, 7-NI treatment did not restore renal function in cirrhotic rats (creatinine clearance: 0.76 ± 0.03 ml · min−1· 100 g body wt−1in cirrhotic rats vs. 0.79 ± 0.05 ml · min−1· 100 g body wt−1in cirrhotic rats+7-NI; P NS.). Taken together, these results indicate that nNOS-derived NO contributes to the development of the hyperdynamic circulation and fluid retention in cirrhosis.

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