a1_We analyzed fiber type composition of soleus and extensor digitorum longus (EDL) muscles of 3- to 19-month-old male and female inbred Lewis rats using histochemical demonstration of mATPase activity. The rats were divided into four groups of the mean age of 3, 6, 9 and 14 months. We found that the soleus muscle of 3-month-old rats contained significantly more of fast 2A fibers and less of slow type 1 fibers compared to older rats, while no significant difference was found between female and male rats at any age group. In contrast, we found no significant difference in the EDL fiber type composition among the age groups, but we found that the EDL muscle of female rats contained significantly less 2A fibers and more 2B fibers than that of male animals. Our results thus revealed an age difference in the soleus muscle and a sex difference in the EDL muscle among postnatal Lewis rats. The number of slow type 1 fibers in the soleus muscle varied between 87 and 100 % and that of 2A fibers between 13 and 0 %. In the EDL the percentage of type 1 fibers varied between 2.6 and 8.7 %, that of 2A fibers between 12.6 and 25.8 % and that of 2B fibers between 70.4 and 81.6 %. Both muscles thus exhibited a considerable degree of variability among individual animals even in the same age group. Furthermore, a comparison of the Lewis rats with literature data of other rat strains showed that the number of fast 2A fibers in the soleus muscle of 4-month-old and older animals decreased in this order: SHR > Lister Hooded > Fisher 344 > Sprague- Dawley > Wistar > WBN/Kob > Lewis strain, being almost 20 % in the SHR and less than 2 % in the Lewis rats. In contrast, the “fastest” composition (judged according to the percentage of the fastest 2B fibers) of the EDL muscle was demonstrated by Lewis, Wistar and Fisher 344 rats (about 75 %), while Sprague-Dawley and WBN/Kob rats contained only about 50 % of 2B fibers., a2_The percentage of slow type 1 fibers in the EDL was low in all strains (about 5 %). Our results thus show that the individual, age and sex as well as inter-strain differences in muscle fiber type composition should not be ignored when comparing results of different studies. We also demonstrated that the inbred Lewis strain appears to have more “specialized” muscle composition, as its soleus is the “slowest” and its EDL is the “fastest” among the routinely used rat strains., P. Novák, G. Zachařová, T. Soukup., and Obsahuje bibliografii a bibliografické odkazy
Induction of the inducible form of nitric oxide synthase (iNOS) in the vascular and cardiac tissue by several inflammatory stimuli may result in the production of large amounts of nitric oxide (NO) for a sustained period. Recent data obtained in the rat aorta in which iNOS was induced by lipopolysaccharide (LPS) have demonstrated that adventitial cells represent the main site of NO production. Adventitial-derived NO can exert an immediate down-regulatory effect on smooth muscle contraction (via activation of the cyclic GMP pathway) but may also initiate longer lasting effects through the formation of NO stores within the medial layer. One candidate for such NO stores are dinitrosyl non-heme iron complexes. Low molecular weight thiols interact with preformed NO stores and promote vasorelaxation by a cyclic GMP-independent mechanism involving the activation of potassium channels. In the heart, the induction of iNOS is involved in delayed protection against ischemia-reperfusion-induced functional damages. Recent data obtained with monophosphoryl lipid A, a non-toxin derivative of LPS, strongly suggest that iNOS-derived NO in the rat heart does not act as an immediate mediator of the cardioprotection but rather as a trigger of long-term protective mechanisms. Thus, the present data reveal the important role of adventitial cells as a site of iNOS expression and activity in intact blood vessels. The induction of adaptive mechanisms in the heart and the formation of releasable NO stores in blood vessels are examples of long-term consequences of iNOS induction. These new information are relevant for a better understanding of the circumstances in which NO overproduction by iNOS may play either a beneficial or deleterious role in these tissues., B. Muller, A. L. Kleschyov, K. Gyorgy, J.-C. Stoclet., and Obsahuje bibliografii
Angiogenesis is known to be triggered by various stimuli including hypertension. It was previously found that NO-deficient hypertension is accompanied by structural remodeling of the cardiac muscle and large coronary arteries. This study was aimed to examine the qualitative subcellular alterations of capillaries in the heart of the rats treated with L-NAME (40 mg/kg/day for 4 weeks). The results showed that long-lasting inhibition of NO production induced an apparent activation of fibroblast function. This was associated with enhancement of fibrozation as well as with the induction of angiogenesis. Accordingly, fibroblasts were frequently located in the vicinity of capillary pericytes, which was followed by their detachment and migration. Moreover, besides inactive or even injured capillaries, the other ones exhibited extensive proteosynthetic activity linked to capillary growth, proliferation and migration of endothelial cells. The results strongly indicate enhanced triggering of the angiogenesis in L-NAME-induced NO-deficient hypertension., Ľ. Okruhlicová, N. Tribulová, I. Bernátová, O. Pecháňová., and Obsahuje bibliografii
MicroRNAs are emerging as important regulators of cardiac function. This study investigated the role of microRNA-24 (miR-24) in ischemic cardiomyocytes, based on the observation that miR-24 expression was significantly enhanced in the ischemic myocardium of rats. Using primary cultured rat cardiomyocytes, cell injury was induced by ischemic conditions, and the cells were evaluated for changes in lactate dehydrogenase (LDH) release, cell viability, apoptosis and necrosis. The results showed that miR-24 was increased in myocytes exposed to ischemia. When miR-24 was further overexpressed in ischemic myocytes using the mimic RNA sequence, LDH release was reduced, cell viability was enhanced, and apoptosis and necrosis rates were both decreased. By contrast, a deficiency in miR-24 resulted in the largest LDH release, lowest cell viability and highest apoptosis and necrosis rates in normal and ischemic myocytes, with significant changes compared to that of non-transfected myocytes. Additionally, the mRNA and protein levels of the pro-apoptotic gene, BCL2L11, were down-regulated by miR-24 overexpression and up-regulated by miR-24 deficiency. The luciferase reporter assay confirmed BCL2L11 to be a target of miR-24. Overall, this study showed a protective role for miR-24 against myocardial ischemia by inhibiting BCL2L11, and may represent a potential novel treatment for ischemic heart disease., D.-F. Li ... [et al.]., and Obsahuje seznam literatury
Primary aldosteronism (PA) is the most common cause of endocrine hypertension with a high frequency of cardiovascular complications. The unfavorable cardiometabolic profile may be due to aldosterone-mediated activation of inflammatory cells, circulatory cytokines and activation of collagen synthesis in the vessel wall. Aim of our study was to evaluate differences in the levels of hsCRP, IL-6, TNF-α and N-terminal propeptide of collagen I (PINP) in patients with PA and essential hypertension (EH) as a control group, and between the subtypes of PA (aldosterone producing adenoma - APA, idiopathic hyperaldosteronism - IHA). We studied 28 patients with PA (IHA - 10 patients, APA - 12 patients, 6 unclassified) and 28 matched patients with EH. There were no differences in the levels of inflammatory markers between the followed groups [EH vs. PA: TNF-α (5.09 [3.68-6.32] vs. 4.84 [3.62-6.50] pg/ml), IL-6 (0.94 [0.70-1.13] vs. 0.97 [0.71- 1.28] pg/ml), hsCRP (0.53 [0.25-1.54] vs. 0.37 [0.31-0.61] mg/l), leukocytes (6.35±1.42 vs. 5.97±1.29 109 l); APA vs. IHA: TNF-α (4.54 [3.62-7.03] vs. 5.19 [4.23-5.27] pg/ml), IL-6 (0.96 [0.63- 1.21] vs. 0.90 [0.65-1.06] pg/ml), hsCRP (0.34 [0.29-0.47] vs. 0.75 [0.36-1.11] mg/l), leukocytes (6.37±1.41 vs. 5.71±1.21 109 l)]. Significant differences in the levels of PINP between PA and EH group were observed (35.18 [28.46-41.16] vs. 45.21 [36.95-62.81] μg/l, p≤0.003). No differences in inflammatory markers were observed between the followed groups, we confirmed higher levels of PINP in patients with PA., Z. Šomlóová, O. Petrák, J. Rosa, B. Štrauch, T. Indra, T. Zelinka, M. Haluzík, V. Zikán, R. Holaj, J. Widimský Jr., and Obsahuje bibliografii
The aim of our study was to test the hypothesis, whether repeated allopurinol pre-treatment (in dose of 135 mg/kg s.c.) can influence changes of brain excitability caused by long-term hypoxia exposition in young immature rats. Rat pups were exposed together with their mother in to an intermittent hypobaric hypoxia (simulated altitude of 7 000 m) since the day of birth till the 11th day (youngest experimental group) or 17th day for 8 hours a day. Allopurinol was administered daily immediately before each hypoxia exposition. The duration of evoked afterdischarges (ADs) and the shape of evoked graphoelements were evaluated in 12, 18, 25 and 35-day-old freely moving male pups. Hypobaric hypoxia prolonged the duration of ADs in 12, 18 and 25-day-old rats. The ADs were prolonged in 35-day-old rats only after the first stimulation. Allopurinol shorted the duration of ADs only in 12-day-old pups. In older experimental group the effect of allopurinol treatment was less pronounced., K. Jandová, ... [et al.]., and Obsahuje seznam literatury
The present study was undertaken to evaluate the use of cortisol 6b-hydroxylation in defining the effect of amiodarone on cytochrome CYP3A activity. To accomplish this goal, the in vivo activity of CYP3A was estimated by measuring the 24-hour urinary excretion of 6b-hydroxycortisol (6b-OHC) and by calculating 24-hour ratio of 6b-hydroxycortisol to urinary free cortisol (6b-OHC/UFC ratio). Nine cardiac patients scheduled for amiodarone treatment were recruited to participate in this study. Urine was collected over a 24-hour period from each subject before the first amiodarone administration and during the third day of oral administration of amiodarone (200 mg four times daily as a loading dose). Three days of amiodarone treatment caused a significant decrease (p<0.05) in both the 6b-OHC/UFC ratio and the 24-hour urinary excretion of 6b-OHC. These results suggest that amiodarone is an inhibitor of CYP3A activity., S. Mičuda, M. Hodač, L. Šišpera, P. Pařízek, M. Pleskot, G. Zimová, J. Cerman, J. Martínková, V. Pinderman., and Obsahuje bibliografii
We studied the effects of administration of b-resorcylidene aminoguanidine (RAG) to Wistar strain rats with experimental diabetes mellitus (DM) induced by streptozotocin. The effects studied included antioxidant levels in plasma and the liver, oxidative damage of lipids represented by the formation of substances reacting with thiobarbituric acid (TBARP) and selected biochemical indicators. The administration of RAG did not significantly affect antioxidant status of diabetic rats or hemoglobin glycation and plasma concentration of fructosamine. In diabetic rats, application of RAG decreased formation of TBARP in plasma but not in the liver. Moderate steatosis of liver and increased plasma levels of triacylglycerols in diabetic rats were significantly improved by application of RAG., A. Liptáková, J. Čársky, O. Uličná, O. Vančová, P. Božek, Z. Ďuračková., and Obsahuje bibliografii
The myocardium examination by MR spectroscopy is very challenging due to movements caused by the cardiac rhythm and breathing. The aim of the study was to investigate the influence of breathing on the quantitative measurement of lipid/water ratios in different groups of volunteers and different measuring protocols. We examined the lipid content of myocardium at 3T using the proton single voxel spectroscopy. Three protocols (free breathing, breath hold and the use of respiratory navigator) controlled by ECG were used for t he examination of 42 adult volunteers including 14 free divers. Spectra were evaluated using jMRUI software. An average content of lipids in the healthy interventricular septum, gained by all protocols was equal to 0.6 %, which is in agreement with other p ublished data. Based on the quality of examinations and the highest technical success, the best protocol seems to be the one containing a respiratory navigator since it is more acceptable by patients. Based on our results and the literature data we can con clude that MR spectroscopy is able to distinguish patients from controls only if their myocardial lipid content is higher than 1.6 % (mean value of lipids plus two standard deviations)., M. Drobny, P. Sedeivy, M. Dezortova, D. Wagnerova, M. Hajek., and Obsahuje bibliografii