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Exogenous Nitric Oxide (exogenous + nitric_oxide)
Selected AbstractsExogenous nitric oxide causes potentiation of hippocampal synaptic transmission during low-frequency stimulation via the endogenous nitric oxide,cGMP pathwayEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2001Christelle L. M. Bon Abstract Nitric oxide (NO) is a putative participant in synaptic plasticity and demonstrations that exogenous NO can elicit the same plastic changes have been taken to support such a role. The experiments, carried out on the CA1 region of rat hippocampal slices, were aimed at testing this interpretation. A major component of tetanus-induced long-term potentiation (LTP) was lost in response to l -nitroarginine, which inhibits NO synthase, and 1H -[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one (ODQ), which inhibits NO-sensitive soluble guanylyl cyclase (sGC). At 0.2 Hz afferent fibre stimulation, exogenous NO produced, concentration-dependently, a synaptic depression that reverted on washout to a persistent potentiation that occluded tetanus-induced LTP. The NO concentrations necessary (estimated in the 100-nm range), however, were mostly supramaximal for stimulating hippocampal slice sGC activity. Nevertheless the potentiation, but not the preceding depression, was blocked by ODQ. l -nitroarginine and an NMDA antagonist were similarly effective, indicating mediation by the endogenous NMDA receptor,NO synthase,sGC pathway. At a concentration normally too low to affect synaptic transmission but sufficient to stimulate sGC (estimated to be 50 nm), exogenous NO reversed the effect of l -nitroarginine and caused a potentiation which was blocked by ODQ. At a concentration inducing the depression/potentiation sequence, NO partially inhibited hippocampal slice oxygen consumption. It is concluded that, at physiological levels, exogenous NO can directly elicit a potentiation of synaptic transmission through sGC, provided that the synapses are suitably primed. At higher concentrations, NO inhibits mitochondrial respiration, which can result in an enduring synaptic potentiation due to secondary activation of the endogenous NO,cGMP pathway. [source] The Anti-Parasitic Effects of Nitric OxideIUBMB LIFE, Issue 10-11 2003Paolo Ascenzi Abstract Endogenous and exogenous nitric oxide (NO) possesses anti-parasitic effects on both Protozoa and Metazoa. However, NO production requires a tight control to limit cytotoxic damage to the host's own cells. The best known parasitic macromolecular targets for NO(-donors) are cysteine proteases, which are relevant in several aspects of the parasite life cycle and parasite-host relationships, and appear as promising targets for anti-parasitic chemotherapy. IUBMB Life, 55: 573-578, 2003 [source] Nitrergic,purinergic interactions in rat distal colon motilityNEUROGASTROENTEROLOGY & MOTILITY, Issue 1 2004K. Van Crombruggen Abstract, Responses of rat distal colon circular muscle strips to exogenous nitric oxide (NO) and adenosine 5,-triphosphate (ATP) and to electrical field stimulation (EFS) were assessed in the absence/presence of various agents that interfere with nitrergic,purinergic pathways. Exogenous NO (10,6 to 10,4 mol L,1) elicited concentration-dependent, tetrodotoxin (TTX)-insensitive relaxations. The soluble guanylyl-cyclase (sGC) inhibitor 1H[1,2,4,]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) reduced duration and amplitude; the small conductance Ca2+ -sensitive K+ (SK)-channel blocker apamin (APA) only shortened the relaxations. ODQ + APA showed a marked inhibitory effect on duration and amplitude. TTX, APA, the NO-synthase inhibitor N(omega)-nitro- l -arginine methyl ester (l -NAME) and the purinergic receptor P2Y antagonist Reactive Blue 2 (RB2) shortened the relaxations by exogenous ATP (10,3 mol L,1) but did not influence the amplitude. ODQ had no effect. TTX + l -NAME did not yield a more pronounced inhibitory effect than TTX alone. The effect of ATP- , -S was similar to that of ATP. Electrical field stimulation (EFS) (40 V, 0.05 ms, 0.5,4 Hz for 30 s) yielded TTX-sensitive relaxations that were not altered by l -NAME, ODQ or RB2. APA shortened the relaxations. l -NAME + APA nearly abolished these relaxations. ODQ + APA and RB2 +l -NAME reduced the duration. These results suggest that distinct sets of small conductance SK-channels are involved in the amplitude and the duration of the relaxations and that NO increases their sensitivity to NO and ATP via guanosine 3,,5,-cyclic monophosphate (cGMP). ATP elicits relaxations via P2Y receptors with subsequent activation of SK-channels and induces neuronal release of NO. Both nitrergic and purinergic pathways must be blocked to inhibit EFS-induced relaxations. [source] Acute physical exercise reverses S -nitrosation of the insulin receptor, insulin receptor substrate 1 and protein kinase B/Akt in diet-induced obese Wistar ratsTHE JOURNAL OF PHYSIOLOGY, Issue 2 2008José R. Pauli Early evidence demonstrates that exogenous nitric oxide (NO) and the NO produced by inducible nitric oxide synthase (iNOS) can induce insulin resistance. Here, we investigated whether this insulin resistance, mediated by S -nitrosation of proteins involved in early steps of the insulin signal transduction pathway, could be reversed by acute physical exercise. Rats on a high-fat diet were subjected to swimming for two 3 h-long bouts, separated by a 45 min rest period. Two or 16 h after the exercise protocol the rats were killed and proteins from the insulin signalling pathway were analysed by immunoprecipitation and immunoblotting. We demonstrated that a high-fat diet led to an increase in the iNOS protein level and S -nitrosation of insulin receptor , (IR,), insulin receptor substrate 1 (IRS1) and Akt. Interestingly, an acute bout of exercise reduced iNOS expression and S -nitrosation of proteins involved in the early steps of insulin action, and improved insulin sensitivity in diet-induced obesity rats. Furthermore, administration of GSNO (NO donor) prevents this improvement in insulin action and the use of an inhibitor of iNOS (l- N6 -(1-iminoethyl)lysine; l -NIL) simulates the effects of exercise on insulin action, insulin signalling and S -nitrosation of IR,, IRS1 and Akt. In summary, a single bout of exercise reverses insulin sensitivity in diet-induced obese rats by improving the insulin signalling pathway, in parallel with a decrease in iNOS expression and in the S -nitrosation of IR/IRS1/Akt. The decrease in iNOS protein expression in the muscle of diet-induced obese rats after an acute bout of exercise was accompanied by an increase in AMP-activated protein kinase (AMPK) activity. These results provide new insights into the mechanism by which exercise restores insulin sensitivity. [source] Platelet aggregation responses are critically regulated in vivo by endogenous nitric oxide but not by endothelial nitric oxide synthaseBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2009C Tymvios Background and purpose:, Although exogenous nitric oxide (NO) clearly modifies platelet function, the role and the source of endogenous NO in vivo remain undefined. In addition, endothelial NO synthase (NOS-3) critically regulates vessel tone but its role in modulating platelet function is unclear. In this paper we have investigated the roles of endogenous NO and NOS-3 in regulating platelet function in vivo and determined the functional contribution made by platelet-derived NO. Experimental approach:, We used a mouse model for directly assessing platelet functional responses in situ in the presence of an intact vascular endothelium with supporting in vitro and molecular studies. Key results:, Acute NOS inhibition by N, -nitro-L-arginine methyl ester hydrochloride (L-NAME) enhanced platelet aggregatory responses to thrombin and platelets were shown to be regulated primarily by NO sources external to the platelet. Elevation of endogenous NOS inhibitors to mimic effects reported in patients with cardiovascular diseases did not enhance platelet responses. Platelet responsiveness following agonist stimulation was not modified in male or female NOS-3,/, mice but responses in NOS-3,/, mice were enhanced by L-NAME. Conclusions and implications:, Platelets are regulated by endogenous NO in vivo, primarily by NO originating from the environment external to the platelet with a negligible or undetectable role of platelet-derived NO. Raised levels of endogenous NOS inhibitors, as reported in a range of diseases were not, in isolation, sufficient to enhance platelet activity and NOS-3 is not essential for normal platelet function in vivo due to the presence of bioactive NO following deletion of NOS-3. [source] Multiple Mechanisms Of Early Hyperglycaemic Injury Of The Rat Intestinal MicrocirculationCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2002H Glenn Bohlen SUMMARY 1. Hyperglycaemia in the vast majority of humans with diabetes mellitus is the end result of profound insulin resistance secondary to obesity. For patients in treatment, hyperglycaemia is usually not sustained but, rather, occurs intermittently. In in vivo studies of the rat intestinal microcirculation, endothelial impairment occurs within 30 min at D -glucose concentrations , 300 mg/dL. Endothelial-dependent dilation to acetylcholine and constriction to noradrenaline is impaired. Vasodilation to exogenous nitric oxide (NO) remains normal. 2. When initiated before hyperglycaemia, suppression of oxygen radicals by both scavenging and pretreatment with cyclo-oxygenase blockade to prevent oxygen radical formation minimized endothelial impairments during hyperglycaemia. Neither treatment was effective in restoring endothelial function once it was damaged by hyperglycaemia. 3. A mechanism that may initiate the arachidonic acid, oxygen radical process is activation of specific isoforms of protein kinase C (PKC). De novo formation of diacylglycerol during hyperglycaemia activates PKC. Blockade of the ,II PKC isoform with LY-333531 prior to hyperglycaemia protected NO formation within the arteriolar wall, as judged with NO-sensitive microelectrodes. Furthermore, once suppression of endothelial dilation was present in untreated animals, PKC blockade could substantially restore endothelial-dependent dilation. 4. These results indicate that acute hyperglycaemia is far from benign and, in the rat, causes rapid endothelial impairment. Both oxygen radical scavenging and cyclo-oxygenase blockade prior to bouts of hyperglycaemia minimize endothelial impairment with limited side effects. Blockade of specific PKC isozymes protects endothelial function both as a pre- or post-treatment during moderately severe hyperglycaemia. [source] Plasma nitrite/nitrate and endothelin-1 concentrations in neonatal sepsisACTA PAEDIATRICA, Issue 5 2003J Figueras-Aloy Aim: To determine the changes in plasma nitrite/nitrate (NOx) and endothelin-1 (ET-1) concentrations during neonatal sepsis. Methods: In a prospective study, 60 consecutive newborns meeting the criteria for sepsis and without receiving exogenous nitric oxide (25 haemoculture-positive [HC+] and 35 haemoculture-negative [HC,]) were compared with 68 healthy newborns (46 full-term and 22 preterm). NOx and ET-1 concentrations were measured in each newborn within 48 h of diagnosis of sepsis and then every third day up to three determinations. SNAP-II and SNAPPE-II severity scores were performed at the moment of highest clinical severity. Results: At the beginning of the sepsis period, controls and septicaemic newborns had similar NOx and ET-1 levels, with the exception of infants with severe HC+ sepsis. Throughout the sepsis period, NOx increased in moderate HC+ sepsis and decreased in HC, sepsis, reaching a significant difference at the end of the study period (59.9 ± 72.7 vs 33.9 ± 15.3 ,mol/L; p= 0.036). Meanwhile, ET-1 in newborns with severe HC+ sepsis remained higher than that in the moderate HC+ sepsis group and HC, group, reaching significant differences in all the periods. The highest ET-1 value was positively correlated with SNAP-II and SNAPPE-II scores. Conclusion: NOx concentrations increased throughout the neonatal HC+ sepsis period, reaching significant differences after 7,9 d. The highest ET-1 levels in neonatal HC+ sepsis emerged before the NOx peak, at 3,5 d, and later decreased. Only newborns with severe HC+ sepsis presented a significant increase in ET-1 concentrations from the beginning of the septicaemic process. [source] | |||||||||||||