Nitric Oxide In Rats Research Articles

Metabolism of nitric oxide under the conditions chronic alcohol intoxication modelling

It was experimentally shown that ethanol affects the production of nitric oxide in rats. However, nitric oxide can have both a protective effect by weakening the harmful effect of ethanol on the microcirculation of the liver, and lead to liver damage by active forms of nitrogen. The purpose of the study is to study changes in the nitric oxide cycle under the conditions of modeling chronic alcohol intoxication in rats. Experiments were performed on 30 white, mature male Wistar rats, weighing 180–220 g. The animals were divided into 2 groups: I – control (n=6); II group – animals with alcoholic hepatitis (n=24) modelled by the method of forced intermittent alcoholization for 5 days, with a repeat after two days by intraperitoneal injection of a 16.5% ethanol solution in a 5% glucose solution, at the rate of 4 ml/kg of body weight. Animals were removed from the experiment on days 10, 14, 21 and 28 by taking blood from the right ventricle of the heart under thiopental anesthesia. The activity of inducible and constitutive isoforms of NO-synthase, concentration of nitrite, nitrosothiols and peroxynitrites of alkali and alkaline earth metals, the activity of nitrite reductase, nitrate reductase and arginase were determined in rat liver homogenate. Chronic alcohol intoxication modelling for 10–28 days leads to a violation of the formation and metabolism of nitric oxide with the predominant formation of its toxic metabolites, such as peroxynitrites and nitrites, which threatens the development of nitrosative stress in the liver. Chronic alcohol intoxication on the 10th–28th days of the experiment is accompanied by a sharp decrease in the activity of the arginase-dependent pathway of arginine metabolism in the liver of rats, which indicates a violation of the deamination processes in the Krebs-Handzeleit cycle. Keywords: nitrites, NO-synthase, peroxynitrite, alcohol, liver, rats.

Effects of Intravesical Electrical Stimulation on Urinary Adenosine Triphosphate and Nitric Oxide in Rats With Detrusor Underactivity Induced By Bilateral Pelvic Nerve Crush Injury: The Possible Underlying Mechanism.

To explore the effect of intravesical electrical stimulation (IVES) on urinary adenosine triphosphate (ATP) and nitric oxide (NO) in rats with detrusor underactivity (DU) induced by bilateral pelvic nerve crush (bPNC), and to determine the underlying peripheral mechanism. Twenty-four female Sprague-Dawley rats were equally divided into 3 groups: sham; bPNC; and IVES. Rats in the IVES group began to receive IVES treatment 10 days after bPNC (20 minutes per day for 14 consecutive days). After the 14th IVES, rat urine was collected and cystometry was performed. The serum creatinine, blood urea nitrogen, and urinary ATP and NO levels were measured, and a routine urinalysis was performed. The maximum cystometric capacity (MCC), maximum changes in bladder pressure during filling (∆FP), and postvoid residual urine (PVR) in the IVES group were significantly lower than the bPNC group, and the maximum changes in bladder pressure during voiding (∆VP) was significantly higher than the bPNC group. Compared with the sham group, the MCC, ∆FP and PVR were significantly increased, and the maximum voiding pressure (MVP) and ∆VP were significantly decreased in the bPNC group. After bPNC, urinary ATP was significantly decreased, and urinary NO was significantly increased. In IVES-treated rats, urinary ATP was significantly higher than the bPNC group, and NO was significantly lower than the bPNC group. In addition, the ATP-to-NO ratio of the rats in the bPNC group was significantly lower than the sham and IVES groups. Correlation analysis showed that the ATP and NO were not correlated with the MCC, ∆FP, MVP, ∆VP, and PVR. Promoting the release of urothelial ATP and inhibiting the release of urothelial NO may be one of the peripheral mechanisms underlying IVES in the treatment of DU. Specifically, IVES may shift the balance between excitation and inhibition toward excitation.

Propofol but not dexmedetomidine produce locomotor sensitization via nitric oxide in rats

The abused potential of some anesthetics has been debated. Measurement of locomotor sensitization is a better way to detect the neurobehavioral plasticity of addiction. The present study aims to explore whether propofol and dexmedetomidine are capable of inducing locomotor sensitization. Male Wistar rats (250-300g) were the subjects (n= 8 for each group). Propofol (20 and 40mg/kg) and dexmedetomidine (2.5-20μg/kg) or saline were injected to rats intraperitoneally (IP), and their locomotor activities were recorded for 15min. Consequently, L-NAME (30 and 60mg/kg)-a nitric oxide (NO) inhibitory agent-was injected to rats 30min before propofol (40mg/kg) or saline injections, and the locomotor activity was recorded. The process was carried out for 13days, with 7 sessions applied every other day. Dexmedetomidine did not produce any significant locomotor sensitization. While propofol (20mg/kg) produced a significant locomotor sensitization in the last treatment session (day 13), at the higher dose, it prompted a significant locomotor sensitization from the 3rd treatment session. L-NAME blocked propofol-induced locomotor hyperactivity and sensitization significantly without producing any noteworthy changes on the locomotor activity during the testing period of 13days when administered alone. Our results suggest that propofol but not dexmedetomidine produced a significant locomotor sensitization via central nitrergic system. Dexmedetomidine may have a lesser psychostimulant type addictive potential than propofol. Sensitization development by propofol implies that this drug might be effective on the neuroadaptive processes associated with a stimulant type of dependence.

N-acetylcysteine protects against diabetic nephropathy through control of oxidative and nitrosative stress by recovery of nitric oxide in rats

The diabetes mellitus (DM) induces several changes, with substantial increase of reactive oxygen species (ROS). The ROS cause damage to systemic and renal microvasculature, which could be one of the mechanisms involved in the development of diabetic nephropathy (DN). The ROS modulate other substances like the nitric oxide (NO), a vasodilator with important role in the renal function. N-acetylcysteine (NAC) is an antioxidant that acts replenishing intracellular cysteine levels, which is essential for glutathione formation. The aim of this study was to evaluate the effect of early or late NAC treatment on oxidative/nitrosative stress in DN progression. All rats were submitted to unilateral nephrectomy and diabetes was induced with streptozotocin. The animals were allocated into six groups: controls that received water (CTL) or NAC (CTL + NAC); diabetic groups that received early or late, water (DM-E; DM-L) or NAC (DM + NAC-E; DM + NAC-L), started on 5th day (early) or 4th week (late) after diabetes induction, during 8 weeks. After NAC treatment, the rats were placed in individual metabolic cages to obtain urine and blood samples for analysis of metabolic profile, renal function, thiobarbituric acid reactive substances (TBARS) and NO. At the end of the protocol, the renal cortex was removed for TBARS, NOS evaluation, antioxidants markers and histology. The DM-E group compared to CTL showed a significant increase in glycemia and proteinuria and impaired renal function; there was a significant increase of TBARS in plasma, urine and renal tissue, and also a significant decrease in plasma NO, which were reverted after early NAC treatment. The eNOS was decreased and iNOS was increased in DM-E vs. CTL, p < 0.05. The early NAC treatment in DM rats reduced proteinuria, creatinine, urea, TBARS and iNOS and, increased creatinine clearance, NO and eNOS, increasing significantly the antioxidant defenses, promoting elevated catalase and glutathione compared to DM-E group, all p < 0.05. The late NAC treatment in diabetic rats vs.DM-E showed reduced proteinuria and TBARS excretion and higher values of creatinine clearance and NO, all statistically significant. Histological analysis of the animals in DM-E or DM-L showed significant tubular changes with degeneration and vacuolization in tubular cells, dilated tubular lumen, intense glycosidic degeneration, and discreet mesangial expansion with interstitial fibrosis area. The DM + NAC-E group showed moderate glycosidic degeneration, however, did not present tubular degeneration or fibrosis. The DM + NAC-L group showed severe glycosidic degeneration, moderate tubular cell degeneration, light and focal dilatation of the tubules, with no fibrosis. Our study showed that NAC protected the diabetic rats against renal injury, probably due to the control of oxidative stress via recovery of the NO bioavailability, showing that early NAC was more effective than late treatment. All these data suggest that NAC may be useful in the adjuvant treatment in a safe way, in the early phase of the disease. Eventually, prolonged treatment, even if it is started later, could change the natural history of the disease, delaying the complications of diabetes in renal tissue.

Concentration-related metabolic rate and behavioral thermoregulatory adaptations to serial administrations of nitrous oxide in rats.

BackgroundInitial administration of ≥60% nitrous oxide (N2O) to rats evokes hypothermia, but after repeated administrations the gas instead evokes hyperthermia. This sign reversal is driven mainly by increased heat production. To determine whether rats will behaviorally oppose or assist the development of hyperthermia, we previously performed thermal gradient testing. Inhalation of N2O at ≥60% causes rats to select cooler ambient temperatures both during initial administrations and during subsequent administrations in which the hyperthermic state exists. Thus, an available behavioral response opposes (but does not completely prevent) the acquired hyperthermia that develops over repeated high-concentration N2O administrations. However, recreational and clinical uses of N2O span a wide range of concentrations. Therefore, we sought to determine the thermoregulatory adaptations to chronic N2O administration over a wide range of concentrations.MethodsThis study had two phases. In the first phase we adapted rats to twelve 3-h N2O administrations at either 0%, 15%, 30%, 45%, 60% or 75% N2O (n = 12 per group); outcomes were core temperature (via telemetry) and heat production (via respirometry). In the second phase, we used a thermal gradient (range 8°C—38°C) to assess each adapted group’s thermal preference, core temperature and locomotion on a single occasion during N2O inhalation at the assigned concentration.ResultsIn phase 1, repeated N2O administrations led to dose related hyperthermic and hypermetabolic states during inhalation of ≥45% N2O compared to controls (≥ 30% N2O compared to baseline). In phase 2, rats in these groups selected cooler ambient temperatures during N2O inhalation but still developed some hyperthermia. However, a concentration-related increase of locomotion was evident in the gradient, and theoretical calculations and regression analyses both suggest that locomotion contributed to the residual hyperthermia.ConclusionsAcquired N2O hyperthermia in rats is remarkably robust, and occurs even despite the availability of ambient temperatures that might fully counter the hyperthermia. Increased locomotion in the gradient may contribute to hyperthermia. Our data are consistent with an allostatic dis-coordination of autonomic and behavioral thermoregulatory mechanisms during drug administration. Our results have implications for research on N2O abuse as well as research on the role of allostasis in drug addiction.

Bryophyllum pinnatum inhibits arginase II activity and prevents oxidative damage occasioned by carbon tetrachloride (CCl4) in rats

Bryophyllum pinnatum (B. pinnatum) (Lam.) Oken is used in tropical Africa for the treatment of several diseases such as kidney and urinary disorders. This study was aimed to evaluate the effect of B. pinnatum on arginase II activity and its prevention against renal oxidative damage occasioned by CCl4 in rats. Rats were randomly divided into six groups; group I served as the control, group II served as carbon tetrachloride (CCl4) intoxicated group, group III–V animals were pre-treated with silymarin (25 mg/kg body weight), 25 mg/kg body weight aqueous extracts of Bryophyllum pinnatum (AEBP) and 50 mg/kg body weight AEBP, respectively, for 14 days, followed by a single injection of CCl4. Group VI rats received AEBP only (50 mg/kg body weight). Results obtained revealed that CCl4 intoxication significantly increased (p < 0.05) the levels of renal markers (serum urea, creatinine and arginase II) in rats when compared to the control group. Further, oxidative stress status appeared in CCl4-intoxicated rats, as evidence by significant elevation in malondialdehyde (MDA), with concomitant decrease in levels of functional sulfhydryl groups (SH), antioxidant enzymes and nitric oxide in rats’ kidney. These adverse changes, due to CCl4 intoxication in rats, were however, prevented by pre-treatment with AEBP leaves (25 and 50 mg/kg body weight). The inhibition of arginase II, as well as increased antioxidant status by AEBP in CCl4-intoxicated rats suggests that B. pinnatum can protect kidney against CCl4-induced oxidative damage.

Plasma corticosterone, epinephrine, and norepinephrine levels increase during administration of nitrous oxide in rats

Nitrous oxide (N2O) is a gaseous drug with abuse potential. Despite its common clinical use, little is known about whether N2O administration activates the HPA axis and/or the sympathetic adrenomedullary system. The goal of this study was to determine whether 60% N2O alters plasma concentrations of corticosterone (CORT), epinephrine (EPI), and norepinephrine (NE) in male Long-Evans rats. A gas-tight swivel assembly in the lid of a gas administration chamber allowed the remote collection of blood samples from an indwelling jugular vein catheter at four time-points: baseline and at 30, 60, and 120 min during a two-hour administration of 60% N2O. Relative to baseline, plasma CORT (n = 9) was significantly elevated at all three time-points during N2O inhalation (mixed model analysis, p = .001) and plasma EPI and NE levels were each significantly elevated (n = 8, p ≤ .001) at the 30 min assessment. EPI then declined and did not differ from baseline at the 60 and 120 min assessments (p > .05) whereas NE remained elevated (120 min, p = .001). Administration of 60% N2O increases circulating CORT, EPI, and NE, supporting N2O as a physiological stressor. An N2O-induced increase in CORT is consistent with the observation that addictive drugs typically activate the HPA axis causing increased plasma levels of glucocorticoids. Allostatic models of drug addiction typically involve stress systems and the possible role of stress hormones in N2O-induced allostatic dysregulation is discussed.

Combination of aerobic exercise and Hibiscus sabdariffa Linn. increased nitric oxide in rats

Background Hypertension and myocardial infarction account for the high rate of mortality globally. Hibiscus sabdariffa (HS) Linn. is rich in antioxidants and previous studies have demonstrated its anti-hypertensive effects. Several studies show that regular physical activity is an important component to reduce cardiovascular mortality. The objective of this study was to evaluate the effects of a combination of aerobic exercise and HS extract on nitric oxide (NO) and endothelin-1 (ET-1) in rats. MethodsAn experimental study was conducted on 36 male Wistar rats, aged 4 weeks and 60-70 g in weight. The interventions were aerobic exercises and HS at 400 mg/kg BW/day administered for 4, 8 and 12 weeks. The rats were randomized into 12 groups: 3 control groups (C4, C8, C12), 3 aerobic exercise groups (A4, A8, A12), 3 HS groups (H4, H8, H12), and 3 combination groups [aerobic exercise and HS] (HA4, HA8, HA12). After 4, 8, and 12 weeks, the rats were sacrificed and their abdominal aorta was collected for determination of nitric oxide and ET-1 concentrations. One way ANOVA was used to analyze the data. ResultsThere was a significant difference in NO levels between all groups, with the 4-week aerobic exercise group (A4) showing the highest NO levels compared to the other eleven groups (p&lt;0.05). In contrast, the ET-1 levels were not significantly different between all groups. Conclusions This study demonstrated that the combination of HS supplementation and aerobic exercise increases NO in rats, and provided further evidence to the traditional use of the plant as an antioxidants agent.

Stimulation of μ-opioid receptors dilates retinal arterioles by neuronal nitric oxide synthase-derived nitric oxide in rats

Opioids contribute to the regulation of cerebral vascular tone. The purpose of this study was to examine the effects of herkinorin, a non-opioid μ-opioid receptor agonist derived from salvinorin A, on blood vessels in the rat retina and to investigate the mechanism underlying the herkinorin-induced retinal vasodilatory response. Ocular fundus images were captured using an original high-resolution digital fundus camera in vivo. The retinal vascular responses were evaluated by measuring the diameter of retinal arterioles in the fundus images. Both systemic blood pressure and heart rate were continuously recorded. Herkinorin increased the retinal arteriolar diameter without significantly changing mean blood pressure and heart rate. The retinal vasodilator response to herkinorin was almost completely prevented following treatment with naloxone, a nonselective opioid receptor antagonist and H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), a selective μ-opioid receptor antagonist. Nω-nitro-L-arginine methyl ester, a nonselective nitric oxide (NO) synthase inhibitor, or indomethacin, a cyclooxygenase inhibitor, significantly attenuated the herkinorin-induced retinal vasodilator responses. In addition, Nω-propyl-L-arginine, an inhibitor of neuronal NO synthase, diminished the herkinorin-induced retinal vasodilator responses. Seven days after an intravitreal injection of N-methyl-D-aspartic acid, loss of inner retinal neurons and abolishment of the retinal vasodilator response to herkinorin were observed. These results suggest that herkinorin dilates rat retinal arterioles through stimulation of retinal μ-opioid receptors. The μ-opioid receptor-mediated retinal vasodilator response is likely mediated by NO generated by neuronal NO synthase. Retinal neurons play an important role in the retinal vasodilator mechanism involving μ-opioid receptors in rats.

Effect of zinc and acetate trigonella foenum graecum on the metabolism of nitric oxide in rats with alcohol dependence formed brain

The influence of zinc acetate and fenugreek (Trigonella foenum) on the metabolism of nitric oxide in the brain of rats with formed alcohol dependence was investigated. To determine the activity of NO-synthase and its' isoforms (cytokine-dependent iNOS and Са 2+ -dependent cNOS) in brains of rats with formed alcohol addiction. To measure the level of NO 2 – , NO 3 – and S-nitrosothioles in brains of rats with formed alcohol addiction. To study the effects of zinc acetate and Fenugreek (Trigonella foenum graecum) on activity of NO-synthase and its' isoforms (cytokine-dependent iNOS and Са 2+ -dependent cNOS) and level of NO 2 – , NO 3 – and S-nitrosothioles in brains of rats with formed alcohol addiction. It was shown that under conditions of consumption of alcohol the appropriate links of NO cycle were activated: NO-synthase (by means of cytokine-dependent iNOS and Ca 2+ -dependent NO-synthase isoforms in terms of initial studies: 1-4 weeks) and NO deposition as nitrosothiols

Tanshinone IIA attenuates bleomycin-induced pulmonary fibrosis in rats.

Idiopathic pulmonary fibrosis is a chronic and progressive fibrotic lung disorder with unknown etiology and a high mortality rate. Tanshinone IIA (Tan IIA) is a lipophilic diterpene extracted from the Chinese herb Salvia miltiorrhiza Bunge with diverse biological functions. The present study was conducted to evaluate the effects of Tan IIA on bleomycin (BLM)-induced pulmonary fibrosis in rats. Rats received an intraperitoneal injection of Tan IIA and normal rats were used as controls. Severe pulmonary edema, inflammation and fibrosis were observed in the BLM-treated rats and the counts of total cells, neutrophils and lymphocytes were significantly increased in the bronchoalveolar lavage fluids of those rats. These pathological changes were markedly attenuated by subsequent treatment with Tan IIA. In addition, BLM-induced increased expression of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, cyclooxygenase-2, prostaglandin E2, malondialdehyde, inducible nitric oxide synthase and nitric oxide in rats, which was also suppressed by Tan IIA injection. The present findings suggest therapeutic potential of Tan IIA for pulmonary fibrosis.

Cisplatin-induced renal toxicity via tumor necrosis factor-α, interleukin 6, tumor suppressor P53, DNA damage, xanthine oxidase, histological changes, oxidative stress and nitric oxide in rats: Protective effect of ginseng

Cisplatin is an effective chemotherapeutic agent successfully used in the treatment of a wide range of solid tumors, while its usage is limited due to its nephrotoxicity. The present study was undertaken to examine the effectiveness of ginseng to ameliorate the renal nephrotoxicity, damage in kidney genomic DNA, tumor necrosis factor-α, interleukin 6, tumor suppressor P53, histological changes and oxidative stress induced by cisplatin in rats. Cisplatin caused renal damage, including DNA fragmentation, upregulates gene expression of tumor suppressor protein p53 and tumor necrosis factor-α and IL-6. Cisplatin increased the levels of kidney TBARS, xanthine oxidase, nitric oxide, serum urea and creatinine. Cisplatin decreased the activities of antioxidant enzymes (GST, GPX, CAT and SOD), ATPase and the levels of GSH. A microscopic examination showed that cisplatin caused kidney damage including vacuolization, severe necrosis and degenerative changes. Ginseng co-treatment with cisplatin reduced its renal damage, oxidative stress, DNA fragmentation and induced DNA repair processes. Also, ginseng diminished p53 activation and improved renal cell apoptosis and nephrotoxicity. It can be concluded that, the protective effects of ginseng against cisplatin induced-renal damage was associated with the attenuation of oxidative stress and the preservation of antioxidant enzymes.

The effects of unripe grape extract on systemic blood pressure and serum levels of superoxide dismutase, malondialdehyde and nitric oxide in rat.

Backgrounds:The new lifestyle increases the incidence of hypertension. In Iranian folk medicine, it is believed that Verjuice obtained by unripe grape (Vitis vinifera) could control blood pressure. We tested the effects of unripe grape extract (UGE) in blood pressure alteration, serum antioxidant level and aorta endothelial permeability in rats.Materials and Methods:Four groups of rats were treated daily by placebo and three different doses of UGE (50, 150 and 300 mg/kg/day). Four weeks later, the animals were anesthetized and catheterized. The direct mean arterial, systolic and diastolic pressures (MAP, SP and DP) were recorded. The endothelial permeability was determined and the serum levels of superoxide dismutase (SOD), malonaldialdehyde (MDA) and nitrite were measured.Results:High dose of UGE increased MAP and SP significantly (P < 0.05) when compared with the control group. Decrease of MDA and increase of SOD and nitrite also were detected statistically in animals treated with high dose of UGE (P < 0.05). No difference in aorta endothelial permeability was observed between the groups.Conclusion:The effect of UGE on blood pressure was dose dependent. High dose of UGE increased MAP and SP although its antioxidant activity was significantly high. Such observation mechanisms need to be defined.

Iron Excess Disturbs Metabolic Status and Relative Gonad Mass in Rats on High Fat, Fructose, and Salt Diets

The aim of this study was to assess the metabolic and physiological changes in rats fed a diet high in fat, fructose, and salt, and with excess iron level. Mineral status was also estimated. Wistar rats were assigned to groups fed either a standard control diet (C) or a diet high in fat, fructose, and salt. The noncontrol diets contained either normal (M) or high level (MFe) of iron. After 6 weeks, the length and weight of the rats were measured, and the animals were euthanized. The kidneys and gonads were collected, and blood samples were taken. Serum levels of insulin, nitric oxide, and iron were measured. The iron, zinc, copper, and calcium concentrations of tissues were determined. It was found that the M diet led to a significant increase in the relative kidney mass of the rats compared with the control group. Among the rats fed the M diet, markedly higher serum level of iron and lower levels of zinc and copper were observed in tissues, while significantly higher calcium levels were found in the gonads. The MFe diet resulted in decreased obesity index, insulin level, and nitric oxide serum concentration in the rats, when compared with both the M and C diets. The high iron level in the modified diet increased the relative mass of the gonads. The excess iron level in the diet disturbed the zinc, copper, and calcium status of tissues. The decrease in insulin and nitric oxide in rats fed the diet high in iron, fat, fructose, and salt was associated with disorders of zinc, copper, and calcium status, as well as with an increase in the relative mass of the gonads.

Vasodilator efficiency of endogenous prostanoids, Ca2+-activated K+ channels and nitric oxide in rats with spontaneous, salt-dependent or NO-deficient hypertension

Hypertension is associated with the imbalance of vasoconstrictor and vasodilator systems. Vasodilation is usually evaluated in isolated blood vessels, but except for nitric oxide (NO), relatively little attention is given to the in vivo efficiency of particular vasodilator mechanisms. The aim of our study was to evaluate the contribution of endogenous vasodilator prostanoids, Ca(2+)-activated K(+) channels and NO to blood pressure (BP) maintenance in rats with three different forms of experimental hypertension. Both principal vasopressor systems (the renin-angiotensin system and the sympathetic nervous system) were blocked by captopril and pentolinium in conscious spontaneously hypertensive rats (SHRs), Dahl salt-hypertensive (DS-HS) rats and rats with NO-deficient hypertension, as well as in their normotensive controls. Thereafter, we monitored BP changes in rats subjected to either a sequential or an isolated blockade of prostanoid synthesis by the non-selective cyclooxygenase inhibitor, indomethacin, of Ca(2+)-activated K(+) channels by tetraethylammonium and of NO formation by N(G)-nitro-L-arginine methyl ester. All three forms of experimental hypertension were characterized by augmented sympathetic vasoconstriction. The vasodilatation exerted by endogenous prostanoids and Ca(2+)-activated K(+) channels was enhanced in all forms of hypertension, almost proportionally to BP elevation. On the contrary, NO-dependent vasodilatation was not enhanced in any form of experimental hypertension, and there was a severe relative NO deficiency in both, SHRs and DS-HS rats. In conclusion, our data suggested that there is a compensatory activation of vasodilator prostanoids and Ca(2+)-activated K(+) channels in rats with experimental hypertension, whereas NO-dependent vasodilatation is not augmented. Thus, the overall activity of vasodilator systems failed to compensate for augmented sympathetic vasoconstriction in hypertensive animals.

Mild hypothermia induced cardioprotection against ischemia/reperfusion injury mediated by nitric oxide in rat isolated heart model

Mild hypothermia induced cardioprotection against ischemia/reperfusion injury mediated by nitric oxide in rat isolated heart model

Effect of Long Term Mobile Phone Exposure on Oxidative-Antioxidative Processes and Nitric Oxide in Rats

ABSTRACTThe effects of radiation emitted from cellular phones on humans are an emerging area of investigation. The previous studies have shown the role of oxidative stress and NO at radiofrequency exposed rats. Therefore, the purpose of this study was to investigate the effect of microwave/radiofrequency emitted from mobile phones and its possible oxidative damage. Wistar Albino rats were divided into three groups as exposure, sham and cage control. Rats in exposure group were exposed to 900 MHz microwave radiation (0.0782 mW/cm2) in a carousel for 2 hours/7 days in a week during ten months. The same process was applied to sham group but the generator was turned off. Rats in cage control group were kept in cage only during the study. The levels of catalase (CAT), myeloperoxidase (MPO), malondialdehyde (MDA), total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI) in liver and nitric oxide (NO) levels in serum were determined to demonstrate the role of oxidative mechanisms. The increase of nitric oxide levels in exposure and sham groups were found significant compared to cage control group (p<0.01, p<0.05). Although serum NO levels increased in exposed rats, the difference between exposure and sham groups was not significant (p>0.05). MDA and TOS levels in liver tissue were found higher in exposed group compared to sham and cage control group (p<0.05). However, no significant alterations were found in other endpoints such as CAT, MPO, TAC and OSI. In this study we showed that 900 MHz radiofrequency radiation emitted from mobile phones exhibited an increase on MDA and TOS levels. Therefore, RF radiation emitted from GSM cellular phone may play a role to induce oxidative damage by increasing lipid peroxidation and oxidative stress.

Torsion/Detorsion of the Testis Does Not Modify Responses to Nitric Oxide in Rat Isolated Penile Bulb

Ischaemia-reperfusion damage induced by torsion/detorsion of the testicles may be a causative factor leading to erectile dysfunction through oxidative stress-dependent changes in the responses of the penile bulb, an erectile tissue of the penis. We aimed at investigating the effects of unilateral testicular torsion/detorsion (2 or 24 hr) treatment on relaxations induced by electrical field stimulation and sodium nitroprusside in rat isolated penile bulb. Male Sprague-Dawley rats used in the study were divided into two groups. The treatment group was subjected to unilateral torsion followed by detorsion for 2 or 24 hr, while the control group underwent only sham operation. For in vitro organ bath experiments, penile bulbs were isolated and responses to relaxant agents and electrical field stimulation (70 V, 1 msec., 0.5-8 Hz, 5 sec.) were recorded on a computer-based data acquisition system via a force displacement transducer. In tissues precontracted with phenylephrine (3 x 10(-6 )M), relaxations induced by electrical field stimulation were not significantly different before and after 2 or 24 hr of detorsion. Similarly sodium nitroprusside- (10(-8)-3 x 10(-6 )M) and papaverine-induced (10(-7)-10(-4 )M) relaxations were also found unchanged in the detorsion group compared to control. In conclusion, spermatic cord torsion did not lead to impairment in nitric oxide-mediated relaxant responses of the rat isolated penile bulb.

Sex difference in norepinephrine surge in response to psychological stress through nitric oxide in rats

Psychological stress elevates blood pressure through sympathetic nerve activation. This pressor response is supposedly associated with cardiovascular events. We investigated a sex difference in the pressor response and norepinephrine surge to cage-switch stress in rats. Wistar male and female rats were catheterized for blood pressure monitoring and blood sampling. Six days post-surgery, the rats were exposed to the cage-switch stress and blood samples were collected at rest and 30 min after the start of the stress. The stress-induced pressor response was greater in the male than in the female rats. The stress significantly increased the norepinephrine level in the male, but not in the female rats. Pre-treatment with N G-nitro- l-arginine methyl ester ( l-NAME), a nitric oxide (NO) synthase inhibitor, attenuated the norepinephrine response significantly in the male rats. There was no sex difference in the endothelial NO synthase expression in the gastrocnemius muscle. However the phosphorylation at serine 1177, a marker for eNOS activation, was higher in the male than in the female rats. These results suggest that NO is involved in the norepinephrine surge to psychological stress in the male rats, but not in the female rats. This is the first report on a sex difference in the norepinephrine surge in response to psychological stress through NO, in association with pressor response.

Injection of l-glutamate into medial prefrontal cortex induces cardiovascular responses through NMDA receptor – nitric oxide in rat

We have reported that l-glutamate ( l-glu) microinjections into ventral portion of medial prefrontal cortex (vMPFC) caused tachycardia and blood pressure increase in unanesthetized rats. In the present study, we report the subtype of vMPFC glutamatergic receptor mediating the response as well as the possible involvement of nitric oxide (NO) in these cardiovascular responses. Microinjection of 200 nL of l-glu (81 nmol) into the vMPFC of unanesthetized rats caused long-lasting pressor and tachycardic responses which were abolished by pretreatment with 4 nmol of the specific NMDA receptor antagonist AP7. The response was not affected by 4 nmol of the non-NMDA receptor antagonist NBQX. Local pretreatment with 80 nmol of the unspecific nitric oxide synthase (NOS) inhibitor NG-nitro- l-arginine methyl ester ( l-NAME) or 0.08 nmol of the specific neuronal NOS (nNOS) inhibitor N ω-Propyl- l-arginine ( N-Propyl) blocked l-glu effects. Microinjection of the NO donor sodium nitroprusside (SNP: 3, 9, 27 or 81 nmol) in the vMPFC caused dose-related long-lasting pressor and tachycardic responses in unanesthetized rats, which were similar to those caused by l-glu. These results suggest that cardiovascular responses evoked by local injection of l-glu into the vMPFC of unanesthetized rats are caused by activation of a local NMDA receptor–NO pathway.