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
Ghrelin, an endogenous ligand for growth hormone secretagogue receptor (GHS-R), has been id entified in the rat and human gastrointestinal tract. Ghrelin has been proposed to play a role in gastric acid secretion. Nitric oxide (NO) was shown as a mediator in the mechanism of ghrelin action on gastric acid secretory function. However, there is a little knowledge about this topic. We have investigated the role of ghrelin in gastric acid secretion and the role of NO as a mediator. Wistar albino rats were used in this study. The pyloric sphincter was ligated through a small midline incision. By the time, saline (0.5 ml, iv) was injected to the control group, ghrelin (20 μg/kg, iv) was injected to the first experimental group, ghrelin (20 μg/kg, iv) +L-NAME (70 mg/kg, sc) was injected to the second group and L-NAME (70 mg/kg, sc) was administered to the third group. The rats were killed 3 h after pylorus ligation; gastric acid secretion, mucus content and plasma nitrite levels were measured. Exogenous ghrelin administration increased gastric acid output, mucus content and total plasma nitrite levels, while these effects of ghrelin were inhibited by applying L-NAME. We can conclude that ghrelin participates in the regulation of gastric acid secretion through NO as a mediator., H. M. Bilgin, C. Tumer, H. Diken, M. Kelle, A. Sermet., and Obsahuje bibliografii a bibliografické odkazy
The aim of this study was to evaluate the role of endogenous histamine in the regulation of reactive hyperaemia (RH) and coronary autoregulation in isolated rat hearts. The basal release of cardiac histamine (perfusion pressure 60 cm H2O) amounted to 100-200 pmol/min/g wL During the first 15 s following 30 s of coronary occlusion, the release of histamine increased about three times and returned to basal levels after approximately 90 s, paralleling the changes of coronary flow (CF). Blockade of Hi-receptors increased basal CF by 23±2 %, significantly reduced blood flow debt and prolonged the duration of RH. Blockade of H2- and H3-receptors produced a significant decline of CF, decreased RH flow and diminished RH by 40±3 %. Blockade of all three classes of histamine receptors indicated that endogenous histamine exerts predominantly vasodilatory effects (mediated by H2- and H3-receptors) on coronary circulation. Histamine-induced vasodilation appears to be NO-dependenL Changes of coronary perfusion pressure from 20 to 120 cm H2O were accompanied by an almost linear decrease of histamine release from about 200 to 40-50 pmol/min/g wL Blockade of histamine receptors decreased, while L-NAME significantly widened the autoregulatory range of the isolated rat heart, reduced CF and release of NO, but reversed the pattern of histamine release leaving the autoregulatory range unaltered, which indicate that endogenous histamine does not play a role in the regulation of coronary autoregulation.
Nitric oxide plays an important role in the control of basal coronary tone and mediation of reactive hyperaemic flow response following short-term coronary occlusion. The results presented in this report indicate that NO is involved in the modulation of coronary autoregulation in isolated rat hearts. Isolated rat hearts exhibit autoregulation of coronary flow (CF) between 50 and 80 cm H2O of coronary perfusion pressure (CPP). Within this autoregulatory range NO release (measured as nitrite) varies from
1.7±0.3 to 2.2±0.7 nmol/min/g wL Below the autoregulatory range it decreases slightly, while above this there is more than a twofold increase. Changes of NO release are accompanied by directly proportional changes of cGMP release. The release of hypoxanthine + xanthine shows a reciprocal relationship to CF values. The inhibition of NO synthesis showed a reciprocal relationship with CF values. Inhibition of NO synthesis by L-NAME (30 /¿mol/l) significantly reduces CF over the entire range of CPP changes (20-120 cm H2O), but much less at lower than at higher pressure values. Therefore, the autoregulatory range is significantly widened to CPP of 40-100 cm H2O. Theophylline (30 yumol/l) reduces CF by 15-25 % throughout the entire range of CPP changes. Hence, the CPP-CF curve is shifted downwards without significant changes of the autoregulatory range. Theophylline-induced reduction of NO release is CPP-dependent: as greater as CPP lower. When L-NAME is coadministered with theophylline, CF is additionally reduced while widened autoregulatory range is shifted to the right
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
It is known that hypertension is accompanied by increased [Na+]i. The functional properties of Na,K-ATPase, which transports the Na+ out and K+ into myocardial cells during the relaxation phase, were investigated in the left ventricle (LV), septum (SV) and the right ventricle (RV) of anesthetized dogs with moderate acute blood pressure elevation elicited by short-term (4-hour) NO synthase inhibition. The NO-insufficiency was induced by administration of an L-arginine analogue, the NG-nitro-L-arginine methyl ester (L-NAME). Concerning the function of Na,K-ATPase under the conditions of lowered NO synthesis, we focused our attention to the binding of Na+ to the enzyme molecule. Activation of the enzyme by increasing Na+ concentrations revealed significant changes in both the maximal velocity (Vmax) and the affinity for Na+ (KNa) in all investigated heart sections. The Vmax increased by 27 % in LV, by 87 % in SV and by 58 % in RV. The KNa value increased by 86 % in LV, by 105 % in SV and by 93% in RV, indicating an apparent decrease in the sensitivity of the Na+-binding site in the Na,K-ATPase molecule. This apparently decreased pump affinity for Na+ together with the increase of Vmax suggest that, during the short-term inhibition of NO synthesis, the Na,K-ATPase is capable of extruding the excessive Na+ from the myocardial cells more effectively at higher [Na+]i as compared to the Na,K-ATPase of control animals., N. Vrbjar, M. Strnisková, O. Pecháňová, M. Gerová., and Obsahuje bibliografii