In the presence of carnosine, anserine, histidine, imidazole and 7-nitro indazole, the early postdenervation depolarization of muscle of about 8 mV was significantly increased by 2.15-4.8 mV. The presence of the imidazole ring in the molecule is apparently necessary for this effect. These compounds also eliminated an NO-mediated protective effect of L-glutamate and carbachol on the depolarization of membrane potential. The presence of imidazole, 7-nitro indazole, carnosine and anserine did not significantly change the effect of an external NO donor, sodium nitroprusside. The structural and fuhctional similarity between imidazole derivatives and the known NO synthase inhibitor, 7-nitro indazole suggests that imidazole, carnosine and anserine might act by inhibiting NO production which is stimulated by glutamate and carbachol.
Nitric oxide (NO) may play a role in the pathophysiology of excitotoxicity. It is also possible that increase in Ca2+ overload and NO-mediated events are involved in neuronal loss during excitotoxicity. Using nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry, we have investigated the effects of melatonin on NADPH-d positive hippocampal neurons after kainic acid (KA) induced excitotoxicity in female rats of Wistar strain. Cytosolic Ca2+ (free calcium) in all the respective experimental groups was also studied. Kainic acid was administered, with a single dose of 10 mg/kg/bw (body weight) to the animals. KA treated rats were given melatonin at a dose of 20 mg/kg/bw (for 14 day). On the last day of treatment, animals were transcardially perfused with 4 % paraformaldehyde under deep thiopental anaesthesia. Cryostat sections (20 µm) were cut and stained for NADPH-d positive neurons. KA exposed animals showed a significantly increased number of NADPH-d positive neurons in the dorsal and ventral blade of the dentate gyrus (DG), hilus, CA1 and CA3 area of hippocampus, with a parallel increase in intracellular free Ca2+ ion concentration, as compared to the control group. KA + melatonin-treated animal groups showed reduced number of NADPH-d positive neurons in DG, hilus, CA1 and CA3 areas and a decline in cytosolic Ca2+ concentration, as compared to KA treated group. Our study suggests that the enhanced levels of cytosolic Ca2+ and nitric oxide (NO) play an important role in kainate induced excitotoxicity. Inhibition of NO production may be another means whereby melatonin can reduce oxidative damage and seems to play important role in neuroprotection., A. Jain, ... [et al.]., and Obsahuje seznam literatury
The aim of this study was to co mpare the levels of the plasma muscle-derived cytokines (myokines) and reactive oxygen and nitrogen species (RONS) after muscle damage triggered by different exercises, and to demonstrate the relationships between RONS, thiol redox status and myokines. Sixteen young men participated in a 90-min run at 65 % VO 2 max (Ex.1) or 90-min run at 65 % VO 2 max finished with a 15-min eccentric phase (Ex.2, downhill running). Plasma samples were collected before and at 20 min, 24 h and 48 h after exercise. The exercise trials significantly elevated the concen trations of plasma hydrogen peroxide (H2O2) and 8-isoprostane at 20 min rest. Myokines IL-6 and IL-10 increased at 20 min rest while IL-1 β and TNF α increased at 24 h rest following both running. Ex.2 caused a significant increase in nitric oxide (NO), IL-6, IL-10 and oxidized glutathione (GSSG) levels. Thiol redox status (GSHtotal-2GSSG/GSSG) decreased by about 30 % after Ex.2 as compared to Ex.1. H 2 O 2 and NO directly correlated with IL-6, IL-10, IL-1 β , TNF α and glutathione. These results show that eccentric work is an important factor that enhances the production of RONS and muscle-derived cytokines, and that there is a possible participation of thiol redox status in the release of myokines to blood., A. Zembron-Lacny, M. Naczk, M. Gajewski, J. Ostapiuk-Karolczuk, H. Dziewiecka, A. Kasperska, K. Szyszka., and Obsahuje bibliografii
Nitric oxide (NO) plays a crucial role not only in regulation of blood pressure but also in maintenance of cardiac autonomic tone and its deficiency induced hypertension is accompanied by cardiac autonomic dysfunction. However, underlying mechanisms are not clearly defined. We hypothesized that sympathetic activation mediates hemodynamic and cardiac autonomic changes consequent to deficient NO synthesis. We used chemical sympathectomy by 6-hydroxydopamine to examine the influence of sympathetic innervation on baroreflex sensitivity (BRS) and heart rate variability (HRV) of chronic NG-nitro-L-arginine methyl ester (L-NAME) treated adult Wistar rats. BRS was determined from heart rate responses to changes in systolic arterial pressure achieved by intravenous administration of phenylephrine and sodium nitroprusside. Time and frequency domain measures of HRV were calculated from 5-min electrocardiogram recordings. Chronic L-NAME administration (50 mg/kg per day for 7 days orally through gavage) in control rats produced significant elevation of blood pressure, tachycardia, attenuation of BRS for bradycardia and tachycardia reflex and fall in time as well as frequency domain parameters of HRV. Sympathectomy completely abolished the pressor as well as tachycardic effect of chronic L-NAME. In addition, BRS and HRV improved after removal of sympathetic influence in chronic L-NAME treated rats. These results support the concept that an exaggerated sympathetic activity is the principal mechanism of chronic L-NAME hypertension and associated autonomic dysfunction., M. Chaswal, S. Das, J. Prasad, A. Katyal, M. Fahim., and Obsahuje bibliografii
The mechanisms and myocardial alterations associated with NO-deficient hypertension are still far from clear. The aim of the present study was to focus on the enzyme histochemical and subcellular changes in the heart of L-NAME treated rats, as well as to examine the influence of captopril treatment. Wistar rats were administered either L-NAME (40 mg/kg/day) alone or together with captopril (100 mg/kg/day) for a period of 4 weeks. A significant increase of blood pressure confirmed the reliability of the model. The results showed that long-lasting L-NAME administration was accompanied by a decrease of endothelial NO-synthase activity and by a significant local decrease of the following enzyme activities: capillary-related alkaline phosphatase, 5’-nucleotidase and ATPase (but not dipeptidyl peptidase IV) and cardiomyocyte-related glycogen phosphorylase, succinic dehydrogenase, ß-hydroxybutyrate dehydrogenase and ATPases. No activity of these enzymes was found in the scar, whereas a marked increase of alkaline phosphatase and dipeptidyl peptidase IV activities was found in the foci of fibrotization. Histochemical changes correlated with subcellular changes, which were characterized by 1) apparent fibroblast activation associated with interstitial/perivascular fibrosis, 2) heterogeneous population of the normal, hypertrophic and injured cardiomyocytes, 3) enhancement of the atrial granules and their translocation into the sarcolemma, and 4) impairment of capillaries as well as by induction of angiogenesis. Similar alterations were also found in the heart of captopril co-treated rats, despite of the significant suppression of blood pressure. The results indicate that NO-deficient hypertension is accompanied by metabolic disturbances and ultrastructural alterations of the heart and these changes are probably not induced by the renin-angiotensin system only., N. Tribulová, Ľ. Okruhlicová, I. Bernátová, O. Pecháňová., and Obsahuje bibliografii
The main pathological condition in patients with impaired wound healing is diabetes mellitus. These patients have significantly low circulating nitric oxide (NO) levels because the stimulatory action of insulin on NO synthesis is absent. Additionally, asymmetric dimethylarginine (ADMA), an inhibitor of NO synthase, is increased owing to the generation of oxidative stress. NO was thought to contribute to wound healing. Hyperbaric oxygen (HBO) treatment is generally used in order to accelerate the healing of wounds. The aim of this study was to determine the changes in plasma procollagen type I and III N-terminal peptides (PINP and PIIINP), total nitrite/nitrate (NOx) and ADMA levels; and to evaluate their relation to healing during the HBO treatment of foot ulcers. Data obtained from 18 diabetic patients before and after the HBO therapy were compared statistically by the Wilcoxon test. NOx was increased in 11 and ADMA was decreased in 12 patients following HBO treatment. Both PINP (32.6±29.4 μg/l vs 44.3±33.4 μg/l) and PIIINP (6.97±3.01 μg/l vs 7.92±2.49 μg/l) were significantly increased (p<0.05). Progressive reductions were observed in wound areas, as assessed by the digital wound imaging. In 12 patients, wounds healed by 50 % or higher; whereas only two subjects had minimal improvements (15 % or less healing). The duration of diabetes correlated negatively with wound healing (r = -498, p<0.05). This study suggests that increased collagen synthesis is associated with wound healing during hyperbaric oxygen therapy. Nitric oxide generation may also contribute to the healing process., F. Gurdol ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The aim of this study was to investigate whether the inhibition of one of the endothelial receptor sites in the rat pulmonary artery (muscarinic, histaminergic, purinergic, a 2-adrenergic) affects the NO-mediated relaxation induced by the activation of the other type of receptors. Acetylcholine (ACh)-, histamine (Hist)-, adenosine (Ade)- , and clonidine (Clon)-induced endothelium-dependent relaxations were reduced by the administration of specific antagonists of muscarinic, H1-histaminergic, purinergic or a 2-adrenergic receptors, respectively. The inhibition of H1-histaminergic receptors by chlorphenyramine did not prevent ACh-induced relaxation. Similarly, the inhibition of muscarinic receptors by atropine did not prevent the relaxations to histamine, adenosine and clonidine. On the other hand, the relaxations induced by acetylcholine, histamine, adenosine or clonidine were regularly reduced by NO-synthase inhibitor NG-nitro-L-arginine methyl ester (10-4 mol/l). These results suggest that the inhibition of NO-synthase abolished arterial relaxations induced by all agonists. After inhibition of one type of the endothelial receptors, the NO-dependent relaxation could still be evoked by activation of one of the others., S. Kyselá, J. Török., and Obsahuje bibliografii
a1_Both divisions of the autonomic nervous system are involved in regulation of urinary bladder function. Several substances, other than noradrenaline and acetylcholine, seem to play important roles in physiology and pathophysiology of lower urinary tract. In the current study, we aimed to examine if there exist interplays between nitric oxide (NO) and autonomic transmitters and if such interactions vary in different parts of the urinary bladder in healthy and cyclophosphamide (CYP)-induced cystitic rats; when administered to the animals (100 mg/kg; i.p.), the cytotoxic CYP metabolite acrolein induces bladder inflammation. In the current study a series of in vitro functional studies were performed on detrusor muscle strip preparations. Stimulation with electrical field stimulation (EFS), methacholine, adenosine 5´-triphosphate (ATP), and adrenaline evoked contractile responses in isolated bladder preparations that were significantly reduced in cyclophosphamide (CYP)-treated rats. While the nitric oxide synthase inhibitor N ω -nitro-L-arginine (L-NNA; 10-4 M) did not affect contractile responses in normal, healthy strip preparations, it significantly increased the contractile responses to EFS, methacholine and adrenaline, but not to ATP, in the bladders from the CYP-treated rats. In the CYP-treated rats, the ATP-evoked relaxatory part of its dual response (an initial contraction followed by a relaxation) was 6-fold increased in comparison with that of normal preparations, whereas the isoprenaline relaxation was halved in the CYP-treated. While L-NNA (10-4 M) had no effect on the isoprenaline-evoked relaxations, it reduced the ATP-evoked relaxations in strip preparations from the bladder body of CYP-treated rats., a2_Stimulation of β2- and β3-adrenoceptors evoked relaxations and both responses were reduced in cystitis, the latter to a larger extent. In the trigone, the reduced ATP-evoked contractile response in the inflamed strips was increased by L-NNA, while L-NNA had no effect on the ATP-evoked relaxations, neither on the relaxations in healthy nor on the larger relaxations in the inflamed trigone. The study shows that both contractile and relaxatory functions are altered in the state of inflammation. The parasympathetic nerve-mediated contractions of the body of the bladder, evoked by the release of ATP and acetylcholine, were substantially reduced in cystitis. The relaxations to β-adrenoceptor and purinoceptor stimulation were also reduced but only the ATPevoked relaxation involved NO., R. Veselá ... [et al.]., and Obsahuje seznam literatury
We report here the in vitro measurements of nitric oxide in the cardiovascular system using a porphyrinic sensor specific for NO. Nitric oxide concentrations were measured directly in different parts of the heart and also in different arteries and veins, ranging from 100 /um to 5 mm in diameter. Highest NO * concentrations were found in the heart and particularly in the areas of aortic and pulmonary valves. The NO * concentration in the arteries was higher than in the veins. A clearcut positive correlation was obtained by plotting the vessel diameter and production of nitric oxide.
We investigated the effects of in vivo treatment with the angiotensin-converting enzyme inhibitor (ACE-I) captopril and/or of in vitro administration of L-arginine on the metabolism and ischemia-reperfusion injury of the isolated perfused rat myocardium. Captopril (50 mg/l in drinking water, 4 weeks) raised the myocardial content of glycogen. After 25-min global ischemia, captopril treatment, compared with the controls, resulted in lower rates of lactate dehydrogenase release during reperfusion (8.58±1.12 vs. 13.39±1.88 U/heart/30 min, p<0.05), lower myocardial lactate contents (11.34±0.93 vs. 21.22±4.28 µmol/g d.w., p<0.05) and higher coronary flow recovery (by 25 %), and prevented the decrease of NO release into the perfusate during reperfusion. In control hearts L-arginine added to the perfusate (1 mmol/l) 10 min before ischemia had no effect on the parameters evaluated under our experimental conditions, presumably because of sufficient saturation of the myocardium with L-arginine. In the hearts of captopril-treated rats, L-arginine further increased NO production during reperfusion and the cGMP content before ischemia. Our results have shown that long-term captopril treatment increases the energy potential and has a beneficial effect on tolerance of the isolated heart to ischemia. L-arginine added into the perfusate potentiates the effect of captopril on the NO signaling pathway., J. Divišová, H. Vavřínková, M. Tutterová, L. Kazdová, E. Meschišvili., and Obsahuje bibliografii