The aim of the present study was to investigate the mechanism of vasorelaxant responses induced by red wine polyphenolic compounds (Provinol). Rings of rat femoral artery with or without functional endothelium were set up in a myograph for isometric recording and precontracted with phenylephrine (10-5 M). Provinol in cumulative doses (10-9 to 10-3 mg/ml) elicited endothelium- and dose-dependent relaxation of the artery with maximal relaxation of 56 % at the concentration of 10-5 mg/ml. The relaxant responses to Provinol correlated well with the increase of NO synthase activity in the vascular tissue after administration of cumulative doses of Provinol (10-9 to 10-3 mg/ml). NG-nitro-L-arginine methylester (L-NAME, 3x10-4 M) significantly attenuated the endothelium-dependent relaxation produced by Provinol. Administration of L-arginine (3x10-5 M) restored the relaxation inhibited by L-NAME. The relaxant responses of Provinol were abolished in the presence of Ca2+-entry blocker, verapamil (10-6 M). Administration of hydrogen peroxide (H2O2) abolished acetylcholine (10-5 M)-induced relaxation of the rat femoral artery, while administration of Provinol (10-5 mg/ml) together with H2O2 helped to maintain the acetylcholine-induced relaxation. Provinol only partially affected the concentration-response curve for the NO donor sodium nitroprusside-induced relaxation in rings without endothelium. In conclusion, Provinol elicited endothelium-dependent relaxation of rat femoral artery by the Ca2+-induced increase of NO synthase activity and by protecting NO from degradation., W. Zenebe, O. Pecháňová, R. Andriantsitohaina., and Obsahuje bibliografii
The present study was focused on regulatory role of nitric oxide on functional properties of the cardiac Na, K-ATPase in three various animal models of hypertension: spontaneously hypertensive male rats (SHR) with increased activity of nitric oxide synthase (NOS) by 60 % (Sh1), SHR with decreased activity of NOS by 40 % (Sh2) and rats with hypertension induced by L-NAME (40 mg/kg/day) with depressed activity of NOS by 72 % (LN). Studying the utilization of energy substrate we observed higher Na, K-ATPase activity in the whole concentration range of ATP in Sh1 and decreased activity in Sh2 and LN. Evaluation of kinetic parameters revealed an increase of Vmax value by 37 % in Sh1 and decrease by 30 % in Sh2 and 17 % in LN. The KM value remained unchanged in Sh2 and LN, but was lower by 38 % in Sh1 indicating increased affinity of the ATP binding site, as compared to controls. During the activation with Na+ we observed increased Vmax by 64 % and increased KNa by 106 % in Sh1. In Sh2 we found decreased Vmax by 40 % and increased KNa by 38 %. In LN, the enzyme showed unchanged Vmax with increased KNa by 50 %. The above data indicate a positive role of increased activity of NOS in improved utilization of ATP as well as enhanced binding of Na+ by the cardiac Na, K-ATPase., J. Vlkovičová, V. Javorková, L. Mézešová, O. Pecháňová, N. Vrbjar., and Obsahuje bibliografii a bibliografické odkazy
Renin-angiotensin system (RAS) plays a key role in the regulation of renal function, volume of extracellular fluid and blood pressure. The activation of RAS also induces oxidative stress, particularly superoxide anion (O2-) formation. Although the involvement of O2- production in the pathology of many diseases is known for long, recent studies also strongly suggest its physiological regulatory function of many organs including the kidney. However, a marked accumulation of O2- in the kidney alters normal regulation of renal function and thus may contribute to the development of salt-sensitivity and hypertension. In the kidney, O2- acts as vasoconstrictor and enhances tubular sodium reabsoption. Nitric oxide (NO), another important radical that exhibits opposite effects than O2-, is also involved in the regulation of kidney function. O2- rapidly interacts with NO and thus, when O2- production increases, it diminishes the bioavailability of NO leading to the impairment of organ function. As the activation of RAS, particularly the enhanced production of angiotensin II, can induce both O2- and NO generation, it has been suggested that physiological interactions of RAS, NO and O2- provide a coordinated regulation of kidney function. The imbalance of these interactions is critically linked to the pathophysiology of salt-sensitivity and hypertension., L. Kopkan, L. Červenka., and Obsahuje seznam literatury
The pathogenesis of arterial hypertension in autosomal dominant polycystic kidney disease (ADPKD) is complex and likely dependent on interaction of hemodynamic, endocrine and neurogenic factors. We decided to evaluate the role of endothelin (ET1) and nitric oxide (NO) in the regulation of arterial blood pressure (BP) and to determine plasma levels of ET1 and NO in the group of patients with ADPKD. The ADPKD group (18 patients, 6 men + 12 women, mean age 44.611.7 years, with creatinine clearancecorrig > 1.1 ml/s) was compared with a control group of 27 healthy volunteers of comparable age. Plasma levels of ET1 assessed by direct RIA determination in the group of ADPKD patients (11.03±1.8 fmol/ml) were significantly increased (p<0.001) in comparison with the control group (2.660.58 fmol/ml), while no significant differences were observed between normotensive and hypertensive patients in the ADPKD group. Serum levels of NO were evaluated according to the determination of serum levels of their metabolites - nitrites/nitrates. Serum levels of NO in the group of ADPKD patients (39.85±6.38 μmol/l) were significantly higher (p<0.05) in comparison with the control group (22.7±1.20 μmol/l), whereas in the ADPKD group no significant differences were observed between normotensive and hypertensive patients. Thus, our study supports the concept of complex alteration of both vasoconstrictor and vasodilator systems in the pathogenesis of arterial hypertension in ADPKD., M. Merta, J. Reiterová, R. Ryšavá, V. Tesař, M. Jáchymová., and Obsahuje bibliografii
A short review on the role of endothelium and nitric oxide (NO) in experimental hypertension is presented in the light of the literature and our own recent findings. Based on these data, it is concluded that even though there is a lot of evidence in favor of the primary and causal association of endothelial dysfunction and NO in experimental hypertension, it seems still more plausible that they are causative in some types of hypertension only. Our own experience rather speaks for a secondary but still an important participation of endothelium in the maintenance and further elevation of high blood pressure. Endothelium plays a key role in the development of organ damages in hypertension., H. Vapaatalo, E. Mervaala, M.-L. Nurminen., and Obsahuje bibliografii
Adaptation to hypoxia is beneficial in cardiovascular pathology related to NO shortage or overproduction. However, the question about the influence of adaptation to hypoxia on NO metabolism has remained open. The present work was aimed at the relationship between processes of NO production and storage during adaptation to hypoxia and the possible protective significance of these processes. Rats were adapted to intermittent hypobaric hypoxia in an altitude chamber. NO production was determined by plasma nitrite/nitrate level. Vascular NO stores were evaluated by relaxation of the isolated aorta to diethyldithiocarbamate. Experimental myocardial infarction was used as a model of NO overproduction; stroke-prone spontaneously hypertensive rats (SHR-SP) were used as a model of NO shortage. During adaptation to hypoxia, the plasma nitrite/nitrate level progressively increased and was correlated with the increase in NO stores. Adaptation to hypoxia prevented the excessive endothelium-dependent relaxation and hypotension characteristic for myocardial infarction. At the same time, the adaptation attenuated the increase in blood pressure and prevented the impairment of endothelium-dependent relaxation in SHR-SP. The data suggest that NO stores induced by adaptation to hypoxia can either bind excessive NO to protect the organism against NO overproduction or provide a NO reserve to be used in NO deficiency., E. B. Manukhina, S. Yu. Mashina, B. V. Smirin, N. P. Lyamina, V. N. Senchikhin, A. F. Vanin, I. Yu. Malyshev., and Obsahuje bibliografii
It has been suggested that increase in acute nitric oxide (NO) or cyclic guanosine monophosphate production may be involved in cardioprotection induced by chronic hypoxia (CH). We studied the effect of NO donor molsi domine and phosphodiesterase type 5 inhibitor sildenafil on myocardial ischemia/reperfusion (I/R) injury in rats adapted to CH. Male Wistar rats were exposed to continuous hypoxia in a normobaric chamber (10 % O 2 , 4 weeks). Rats received either saline, mol sidomine (10 mg/kg body weight, i.v.) or sildenafil (0.7 mg/kg body weight, i.v.) 30 min before ischemia. Control rats were kept under normoxia and treated in a corresponding manner. Adaptation to CH increased the myocardial ischemic tolerance. Acute treat ment with either molsidomine or sildenafil significantly reduced infarct size in normoxic rats and further enhanced cardioprotection induced by CH. However, the cardioprotective effect of CH on I/R injury was not additive to the cardioprotection provided b y the drugs., P. Alánová, F. Kolář, B. Ošťádal, J. Neckář., and Obsahuje bibliografii
We studied the response of several parameters related to oxidative stress in the liver of aging rats. Male Wistar rats aged 1.5, 3, 18 and 24 months were used. Livers showed an increase in superoxide anion (O2-) concentration at 1.5 and 18 months of age compared to the 3-month-old group; a decrease in superoxide dismutase (SOD) was seen at 1.5 months and catalase concentrations remained unaltered throughout the aging process. Nitric oxide (NO) progressively declined with age; a significant decrease was particularly apparent at 18 and 24 months of age. Thiobarbituric acid reactive substances (TBARS) decreased significantly at 1.5 months, whereas it increased at 18 and 24 months of age. Concentrations of prostaglandin E2 (PGE2), and adenine nucleotides, and their metabolites, remained unchanged throughout the aging process. Although the mitochondrial damage caused by oxidative stress can result in reduced ATP production and compromised cell function, our results on adenosine nucleotides and their metabolites support the notion that the integrity of mitochondria and enzymatic activity remain mostly unchanged with aging. In conclusion, we observed a significant decrease in the levels of NO in the older groups of rats and hence in its antioxidant activity. This could explain the observed increase in lipid peroxides which suggests an important role for NO in oxidative stress in the liver of older rats., F. Mármol ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Two mechanisms contribute in the development of pulmonary hypertension in pulmonary embolism (PE) - obstruction of pulmonary blood vessels and vasoconstriction. We hypothesize that hypoxia, increased shear stress and/or activation of gathered leukocytes in the PE may cause a release of reactive oxygen species (ROS). Therefore our aim was to determine the influence of the ROS scavenger Tempol on pulmonary hypertension and to d escribe NO synthase activity and production of NO oxidative products (NOx) after PE. In general anesthesia sephadex microspheres suspended in PSS were applied in right jugular vein as the pulmonary microembolism. Than we measured in isolated salt solution -perfused lungs the changes in perfusion pressure, activity of NO synthase and NOx plasma concentration in 7 groups of rats: C: control group (n=5), CN: C + sodium nitroprusside (SN) (n=5), EN: PE + SN (n=5), ETN: Tempol + PE + SN (n=5), CL : C + L -NAME (n=5 ), EL: PE + L-NAME (n=5), ETL: Tempol + PE + L -NAME (n=5). Tempol was applied intraperitoneally before PE. Animals that received Tempol (groups TN, TL) had significantly lower basal perfusion pressure than those which did not rec eive Tempol (EN, EL). Overa ll we measured a higher decrease of perfusion pressure than in the control group (C) after applica tion of SN. Administration of L-NAME after PE (EL) increased the pressure more than in the control group (NL). NOx concentration was higher after PE. We found that preventive administration of Tempol decreases the increase in perfusion pressure after PE. PE increased NO release and concentration of NOx., R. Mizera, D. Hodyc, J. Herget., and Obsahuje bibliografii
As wine polyphenols were show n to possess many positive effects in mammals, including improvement of vascular function, this study investigated the effect of the Slovak Alibernet red wine extract (AWE) on blood pressure and vascular function in young normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Six weeks old, male, WKY and SHR were treated with AWE for three weeks at the dose of 24.2 mg/kg/day. Blood pressure (BP), determined by tail-cuff plethysmography, was significantly elevated in SHR vs. WKY and AWE failed to affect it. Lipid peroxidation was evaluated by determination of thiobarbituric acid-reactive substances. Vascular function was assessed in rings of the femoral artery using Mulvany-Halpern’s myograph. Maximal endothelium-dependent acetylcholine (ACh)-induced rela xation was reduced in control SHR vs. WKY rats by approximatel y 9.3 %, which was associated with a significant decrease of its NO-independent component. AWE failed to affect maximal AC h-induced relaxation, both its NO-dependent and independen t components, compared to controls of the same genotype. AWE however reduced lipid peroxidation in the left ventricle of both WKY and SHR and in the liver of SHR. In conclusion, three-week administration of AWE failed to reduce BP and to improve endothelial function in the femoral arteries of both genotypes investigated., P. Bališ ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy