Principal vasoactive systems - renin-angiotensin system (RAS), sympathetic nervous system (SNS), nitric oxide (NO) and prostanoids - exert their vascular effects through the changes in calcium levels and/or calcium sensitization. To estimate a possible modulation of calcium sensitization by the above vasoactive systems, we studied the influence of acute and chronic blockade of particular vasoactive systems on blood pressure (BP) changes elicited in conscious normotensive rats by acute dose-dependent administration of Rho-kinase inhibitor fasudil. Adult male chronically cannulated Wistar rats were used throughout this study. The acute inhibition of NO synthase (NOS) by L-NAME enhanced BP response to fasudil, the effect being considerably augmented in rats deprived of endogenous SNS. The acute inhibition of prostanoid synthesis by indomethacin modified BP response to fasudil less than the acute NOS inhibition. The chronic NOS inhibition caused moderate BP elevation and a more pronounced augmentation of fasudilinduced BP changes compared to the effect of acute NOS inhibition. This indicates both short-term and long-term NOdependent attenuation of calcium sensitization. Long-term inhibition of RAS by captopril caused a significant attenuation of BP changes elicited by fasudil. In contrast, a long-term attenuation of SNS by chronic guanethidine treatment (in youth or adulthood) had no effect on BP response to fasudil, suggesting the absence of SNS does not affect calcium sensitization in vascular smooth muscle of normotensive rats. In conclusion, renin-angiotensin system contributes to the long-term increase of calcium sensitization and its effect is counterbalanced by nitric oxide which decreases calcium sensitization in Wistar rats., A. Brunová, M. Bencze, M. Behuliak, J. Zicha., and Obsahuje bibliografii
Prolonged exposure to alveolar hypoxia induces physiological changes in the pulmonary vasculature that result in the development of pulmonary hypertension. A hallmark of hypoxic pulmonary hypertension is an increase in vasomotor tone. In vivo, pulmonary arterial smooth muscle cell contraction is influenced by vasoconstrictor and vasodilator factors secreted from the endothelium, lung parenchyma and in the circulation. During chronic hypoxia, production of vasoconstrictors such as endothelin-1and angiotensin II is enhanced locally in the lung, while synthesis of vasodilators may be reduced. Altered reactivity to these vasoactive agonists is another physiological consequence of chronic exposure to hypoxia. Enhanced contraction in response to endothelin-1 and angiotensin II, as well as depressed vasodilation in response to endothelium-derived vasodilators, has been documented in models of hypoxic pulmonary hypertension. Chronic hypoxia may also have direct effects on pulmonary vascular smooth muscle cells, modulating receptor population, ion channel activity or signal transduction pathways. Following prolonged hypoxic exposure, pulmonary vascular smooth muscle exhibits alterations in K+ current, membrane depolarization, elevation in resting cytosolic calcium and changes in signal transduction pathways. These changes in the electrophysiological parameters of pulmonary vascular smooth muscle cells are likely associated with an increase in basal tone. Thus, hypoxia-induced modifications in pulmonary arterial myocyte function, changes in synthesis of vasoactive factors and altered vasoresponsiveness to these agents may shift the environment in the lung to one of contraction instead of relaxation, resulting in increased pulmonary vascular resistance and elevated pulmonary arterial pressure., L. A. Shimoda, J. S. K. Sham, J. T. Sylvester., and Obsahuje bibliografii
Diabetes mellitus is characterized by oxidative stress, which in turn determines endothelial dysfunction. Gliclazide is a sulphonylurea antidiabetic drug with antioxidant effects due to its azabicyclo-octyl ring. It has been reported to potentially protect the vasculature through improvements in plasma lipid levels and platelet function. We hypothesized that gliclazide has a beneficial effect on endothelial function in Goto-Kakizaki rats (GK), an animal model of type 2 diabetes fed an atherogenic diet for 4 months. We evaluated the influence of gliclazide on both metabolic and oxidative status and NO-mediated vasodilation. GKAD rats showed increased oxidative stress and impaired endothelium-dependent vasodilation. GKAD rats treated with gliclazide showed increased sensitivity to NO-mediated vasodilation, a significant decrease in fasting glycemia and insulinemia, and a significant decrease in systemic oxidative stress. In conclusion, our results suggest that gliclazide treatment improves NO-mediated vasodilation in diabetic GK rats with dyslipidemia probably due to its antioxidant effects, although we cannot rule out substantial benefits due to a reduction in fasting blood glucose. The availability of a compound that simultaneously decreases hyperglycemia, hyperinsulinemia, and inhibits oxidative stress is a promising therapeutic candidate for the prevention of vascular complications of diabetes., C. M. Sena ... [et al.]., and Obsahuje seznam literatury
The aim of this study was to evaluate the association of single nucleotide polymorphisms (SNPs) T-786C and G894T in the gene encoding eNOS with blood pressu re variability (BPV) in man. Blood pressure was recorded beat-t o-beat at rest three times in periods of one week (5 min, Finapres, breathing at 0.33 Hz) in 152 subjects (19-24 years). Systolic (SBPV0.1r/SBPV 0.1a) and diastolic (DBPV0.1r/DBPV 0.1a) blood pressure variabilities in relative (r.u.) and absolute (mmHg2/Hz) units were determined by the spectral method as spectral po wer at the frequency of 0.1 Hz. Genotypes of both polymorphisms were detected using polymerase chain reaction and re striction analysis using enzymes Msp I and Ban II. Significant diffe rences were observed in BPV among genotypes of T-786C SNP (p<0.05; Kruskal-Wallis), and among haplotypes of both SNPs (p<0.05; Kruskal-Wallis) as well. In T-786C SNP, carriers of less frequent allele (CC homozygotes and TC heterozygotes) showed significantly greater SBPV0.1r and SBPV0.1a compared to TT homozygote s (Mann-Whitney; p<0.05). The G894T variant showed no sign ificant differences, but, both SNPs were in linkage disequilib rium (D’=0.37; p<0.01). Carriers of haplotype CT/CT (CC homozygotes of -786C/T and TT homozygotes of G894T) displaye d significantly greater SBPV0.1r, SBPV0.1a and DBPV0.1a compared to carriers of other haplotype combinations (Kruskal-Wallis; p=0.015, p=0.048, and p=0.026, respectively). In conclusion, the haplotype formed by less frequent alleles of both eNOS variants was associated with increased systolic and diastolic BPV in this study., M. Jíra ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The production of the pineal hormone melatonin is synchronized with day-night cycle via multisynaptic pathway including suprachiasmatic nucleus linking several physiological functions to diurnal cycle. The recent data indicate that impaired melatonin production is involved in several cardiovascular pathologies including hypertension and ischemic heart disease. However, the mechanisms of melatonin effect on cardiovascular system are still not completely understood. The activation of melatonin receptors on endothelial and vascular smooth muscle cells and antioxidant properties of melatonin could be responsible for the melatonin effects on vascular tone. However, the data from in vitro studies are controversial making the explanation of the melatonin effect on blood pressure in vivo difficult. In vivo, melatonin also attenuates sympathetic tone by direct activation of melatonin receptors, scavenging free radicals or increasing NO availability in the central nervous system. The central and peripheral antiadrenergic action of chronic melatonin treatment might eliminate the mechanisms counter-regulating decreased blood pressure, providing thus additional cardioprotective mechanism. The extraordinary antioxidant activity and antilipidemic effects of melatonin may enhance the modulation of blood pressure by melatonin and probably play the most important role in the amelioration of target organ damage by chronic melatonin treatment. Further investigation of these mechanisms should provide novel knowledge about pathophysiological mechanisms of cardiovascular diseases, additional explanation for their circadian and seasonal variability and potentially generate new impulses for the development of therapeutic arsenal., Ľ. Paulis, F. Šimko., and Obsahuje bibliografii a bibliografické odkazy
We studied the effects of the H2S donor Na2S on the mean arterial blood pressure (MAP) and heart and breathing rates of anesthetized Wistar rats in the presence and absence of captopril. Bolus administration of Na2S (1-4 μmol/kg) into the right jugular vein transiently decreased heart and increased breathing rates; at 8-30 μmol/kg, Na2S had a biphasic effect, transiently decreasing and increasing MAP, while transiently decreasing heart rate and increasing and decreasing breathing rate. These results may indicate independent mechanisms by which H2S influences MAP and heart and breathing rates. The effect of Na2S in decreasing MAP was less pronounced in the presence of captopril (2 μmol/l), which may indicate that the renin-angiotensin system is partially involved in the Na2S effect. Captopril decreased H2S-induced NO release from S-nitrosoglutathione, which may be related to some biological activities of H2S. These results contribute to the understanding of the effects of H2S on the cardiovascular system., M. Drobná, A. Misak, T. Holland, F. Kristek, M. Grman, L. Tomasova, A. Berenyiova, S. Cacanyiova, K. Ondrias., and Obsahuje bibliografii
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