Hypertension is the risk factor of serious cardiovascular diseases, such as ischemic heart disease and atherosclerosis. The aim of the present study was to analyze the development of cardiac tolerance to ischemia in neonatal spontaneously hypertensive rats (SHR) and possible protective effect of ischemic preconditioning (IP) or adaptation to intermittent high-altitude hypoxia (IHAH). For this purpose we used 1- and 10-day-old pups of SHR and their normotensive control Wistar Kyoto rats (WKY). Isolated hearts were perfused in the Langendorff mode with Krebs-Henseleit solution at constant pressure, temperature and rate. Cardiac tolerance to ischemia was expressed as a percentage of baseline values of developed force (DF) after global ischemia. IP was induced by three 3-min periods of global ischemia, each separated by 5-min periods of reperfusion. IHAH was simulated in barochamber (8 h/day, 5000 m) from postnatal day 1 to 10. Cardiac tolerance to ischemia in 1-day-old SHR was higher than in WKY. In both strains tolerance decreased after birth, and the difference disappeared. The high cardiac resistance in 1- and 10-day-old SHR and WKY could not be further increased by both IP and adaptation to IHAH. It may be concluded that hearts from newborn SHR are more tolerant to ischemia/reperfusion injury as compared to age-matched WKY; cardiac resistance decreased in both strains during the first ten days, similarly as in Wistar rats., Z. Charvátová, ... [et al.]., and Obsahuje seznam literatury
Pyridoxal isonicotinoyl hydrazone (PIH) is a new tridentate Fe-chelating agent that should be very promising in many pathological states resulting from both an iron-overload and formation of free radicals. The aim of our study was to investigate the effect of PIH on the cardiovascular system focusing to the regulatory protein - cardiac troponin T (cTnT). The study was carried out in two groups of Chinchilla male rabbits: 1) PIH (50 mg/kg dissolved in 10 % Cremophor i.p., once a week, 10 administrations, n=8) and 2) Cremophor (2 ml/kg i.p. in the same schedule, n=7). Plasma concentrations of cTnT (as a marker of myocardial damage) were measured using a commercial kit (Roche). cTnT was within the physiological range (i.e. < 0.1 mg/l) during the whole experiment in the Cremophor group. In the PIH group, the cTnT levels were not significantly increased when compared with the control group or with the initial values (except with those before the 5th administration). Furthermore, we analyzed the cytosolic and myofibrillar fraction of cTnT in the left ventricular myocardium. Using SDS-PAGE and Western blot we resolved three isoforms. The profiling of TnT did not differ significantly between the PIH-treated group and the Cremophor-treated group. Our data concerning cTnT support the opinion that the possible cardiotoxicity of PIH is very low., M. Adamcová, J. Macháčková, V. Geršl, V. Pelouch, T. Šimůnek, I. Klimtová, R. Hrdina, P. Poňka., and Obsahuje bibliografii
This study was undertaken to examine the effects of dietary supplementation of cysteine and taurine in rats with diabetes induced with streptozotocin (STZ, 65 mg/kg body weight). Experimental animals were treated orally (by gavage) with cysteine (200 mg/kg) and taurine (400 mg/kg), alone or in combination, daily for 8 weeks. In one group, rats were also pretreated 3 weeks before the induction of diabetes (prevention arm) whereas in the other, the treatment was started 3 days after the induction of diabetes (reversal arm). Diabetes increased heart weight/body weight (HW/BW) ratio, plasma glucose, triglyceride and cholesterol levels as well as depressed heart rate (HR), blood pressure, left ventricular systolic pressure (LVSP), rate of contraction (+dP/dt), rate of relaxation (-dP/dt), fractional shortening (FS) and cardiac output (CO). The left ventricular internal diameter in systole (LViDs) was increased whereas that in diastole (LViDd) was decreased. In the prevention arm, treatment of the diabetic animals with cysteine or taurine decreased HW/BW ratio and improved HR, FS, +dP/dt and -dP/dt, as well as normalized LViDs, without altering the increase in glucose level. Cysteine decreased plasma triglyceride and cholesterol levels and improved LVSP whereas CO was improved by taurine. In the reversal arm, cysteine alone or with taurine did not correct the changes in hemodynamic parameters, FS and plasma triglycerides. Diabetes-induced cardiac dysfunction and increases in plasma triglycerides can be prevented, but not reversed, by dietary cysteine alone or in combination with taurine., P. S. Tappia, ... [et al.]., and Obsahuje seznam literatury
The aim of our study was to evaluate a possible association between microalbuminuria (MA), several low-grade inflammation factors and left ventricular hypertrophy (LVH) by using a pharmacological approach. This may provide new insights into the pathophysiologic mechanisms of the cardiorenal syndrome (CRS) linking early renal impairment with elevated cardiovascular risk. Two kidney-one clip (2K-1C) renovascular hypertension was induced in 24 male Wistar rats (220-250 g). After the development of hypertension, rats were divided into four groups: 2K-1C (untreated), calcium channel blocker (amlodipine-treated), angiotensin receptor blocker (losartan-treated) and peripheral vasodilator (hydralazine-treated), which were treated for 10 weeks. Rats in the 2K-1C group had all developed hypertension, a significant increase in plasma levels of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), brain natriuretic peptide (BNP) and C-reactive protein (CRP). Moreover MA and creatininaemia underwent a significant increase. Under treatment decreases were observed in systolic blood pressure (SBP), TNF-α, CRP, IL-6, BNP concentrations and creatininaemia. These results were related to the absence of MA which was significantly associated with reductions in cardiac mass and hypertrophy markers (BNP and β-MHC gene expression) as well as renal interstitial inflammation. In conclusion, our results suggest that the reduction of MA is correlated with the decrease of the inflammatory components and seems to play an important role in protecting against cardiac hypertrophy and renal injury., M. Moubarak , H. Jabbour , V. Smayra , E. Chouery , Y. Saliba , V. Jebara , N. Farés., and Obsahuje seznam literatury
a1_The question was addressed of how nitric oxide synthase (NO synthase) inhibition-induced hypertension in rat parents would affect the cardiovascular system in their offsprings. Two experimental groups were set up: Group I - offsprings of parents who had both been administered NO synthase inhibitor L-nitro-arginine methyl ester (L-NAME 40 mg/kg/day) for 5 weeks, the treatment of dams continued till week 12. Group II - offsprings fed by dams administered L-NAME after delivery only for a period of 4 weeks. Control age-matched offsprings formed the third group. Blood pressure and heart rate in parents and in 3-week-old offsprings were determined noninvasively. In the offsprings, body and heart weight were measured and the heart/body weight ratio (HW/BW) was calculated. The NO synthase activity, and also ornithine decarboxylase activity as a marker of polyamine production, were determined in the heart. The acetylcholine-induced relaxation of aortic rings was also followed. A marked blood pressure increase with a tendency to a decreased heart rate was found in the offsprings of Group I. A significant decrease in heart weight and body weight with a decreased HW/BW ratio indicated cardiac hypotrophy that contrasted with the decrease in NO synthase activity and increase in ornithine decarboxylase activity in the heart. Noteworthy was also the finding of completely preserved relaxation of the aorta to acetylcholine. Offsprings of Group II were similarly characterized by significantly higher blood pressure, a tendency to decreased heart rate, a decrease in heart weight, but not of the HW/BW ratio. The contrasting findings of heart weight decrease on the one hand and NO synthase activity decrease and ornithine decarboxylase increase on the other, were also found in this group. Full relaxation of the aorta to acetylcholine was preserved., a2_It can be concluded that remarkable alterations in the cardiovascular system were found in offsprings of hypertensive NO compromised parents., M. Gerová, I. Bernátová, J. Török, M. Juráni., and Obsahuje bibliografii
UVB radiation from sunlight induces an acute corneal inflammation, photokeratitis, accompanied by changes in corneal hydration. We employed a method of ultrasonic pachymetry for daily examination of central corneal thickness as an index of corneal hydration of the rabbit cornea repeatedly irradiated by UVB radiation (312 nm, daily dose of 0.25 J/cm2 during three or four days) as influenced by UVB absorber (actinoquinol combined with hyaluronic acid) dropped on the ocular surface during irradiation. One day after the third irradiation procedure the animals were sacrificed and corneas examined immunohistochemically for peroxynitrite formation, a marker of oxidative damage, the antioxidant aldehyde dehydrogenase 3A1 and endothelial nitric oxide synthase, an enzyme generated nitric oxide. Results show that UV absorber combined with hyaluronic acid protected the cornea against UVB-induced changes in corneal thickness and microscopical disturbances to the cornea (both seen after buffered saline application) until the fourth experimental day. These UVB doses are equivalent to a daily exposure of 2.5 hrs of the human cornea to solar UVB radiation for three consecutive days. It is suggested that actinoquinol/ hyaluronic acid drops might be helpful for the human eye in the defence against photooxidative and other oxidative processes. and Obsahuje seznam literatury
Changes in extracellular space (ECS) diffusion parameters, DC potentials and extracellular potassium concentration were studied during single and repeated cortical spreading depressions (SD) in 13-15 (P13-15), 21 (P21) and 90-day-old (adult) Wistar rats. The real-time iontophoretic method using tetramethylammonium (TMA+)-selective microelectrodes was employed to measure three ECS parameters in the somatosensory cortex: the ECS volume fraction α (α = ECS volume/total tissue volume), ECS tortuosity λ (increase in diffusion path length) and the nonspecific TMA+ uptake k’. SD was elicited by needle prick. SD was significantly longer at P13-15 than at P21 and in adults. During SD, α in all age groups decreased from 0.21-0.23 to 0.05-0.09; λ increased from 1.55-1.65 to 1.95-2.07. Ten minutes after SD, α (in adults) and λ (all age groups) increased compared to controls. This increase persisted even 1 hour after SD. When SD was repeated at 1 hour intervals, both α and λ showed a gradual cumulative increase with SD repetition. Our study also shows that cortical SD is, as early as P13, accompanied by severe ECS shrinkage and increased diffusion path length (tortuosity) with values similar to adults, followed by a long-lasting increase in ECS volume and tortuosity when compared to pre-SD values., T. Mazel, F. Richter, L. Vargová, E. Syková., and Obsahuje bibliografii
This study was designed to investigate histological changes in skin tissue accompanying immobilization-induced hypersensitivity. Changes in mechanical sensitivity, epidermal thickness, and peripheral nerve profiles in the upper dermis were examined in glabrous skin of rat hind paw after 1, 2, and 4 weeks of ankle joint immobilization by plaster casts. Induction of mechanical hypersensitivity was confirmed after 2 and 4 weeks of joint immobilization. Epidermal thinning and increase in peripheral nerve profiles were observed in skin tissues in immobilized rats. The time course of epidermal thinning and increase in peripheral nerve profiles were similar closely to that of hypersensitivity, with significant differences between the immobilized and control rats after 2 weeks of immobilization, which became even more remarkable at 4 weeks of immobilization. These findings suggest that joint immobilization by cast induces epidermal thinning and increases peripheral nerve profiles in the upper dermis and that these changes might be partly responsible for immobilization-induced hypersensitivity., J. Nakano, ... [et al.]., and Obsahuje seznam literatury
The role of the cortico-tectal pathways in the processing of auditory signals was investigated by recording the click-evoked responses and extracellular multiple unit activity in the inferior colliculus (IC) after functional ablation of the auditory cortex (AC) by local intracortical application of a sodium channel blocker, tetrodotoxin (TTX). Click-evoked IC responses (IC-ER) and multiple unit activity in response to tone bursts were recorded with implanted electrodes in the IC of rats lightly anaesthetized with xylazine. Neural activity was recorded before and after the application of TTX into the ipsilateral auditory cortex (AC) through three implanted cannulas in a total dose of 30 ng. The functional status of the AC was monitored by recording click-evoked middle latency responses from a ball electrode implanted on the AC. During inactivation of the AC, IC-ER amplitudes were either increased (48 % of the cases), decreased (32 % of the cases) or not evidently changed (20 % of the cases). Corresponding effects were observed in the firing rate of IC neurons. Functional ablation of the AC also resulted in a significant prolongation of the latencies of individual waves of the IC-ER. However, the discharge pattern of the multiple unit responses, response thresholds and tuning were not altered during AC inactivation. IC neural activity recovered within several hours, and maximally during 2 days. The results reveal principles of the interaction of cortico-tectal pathways with IC neuronal activity., F. C. Nwabueze-Ogbo, J. Popelář, J. Syka., and Obsahuje bibliografii
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