Academic literature on the topic 'Spontánne hypertenzné potkany'

The aim of this thesis was to evaluate the effect of increased intake of selenium from the diet of rats with spontaneous hypertension (SHR) on other essential elements. The effect of different diets on the element levels in kidney, liver, testes, and blood of rats was observed under model conditions. Tested rats were divided into five groups, where the first group A was the reference group and feed mixture contained no additive. In groups B and C was soybean meal replaced by defatted rapeseed and into feed mixture of group C was additionally added vitamin E. Diet groups D and E contained added selenium and zinc, and group E contained additionally vitamin E in comparison to reference group A. Se content in kidney, liver, testicles, and blood of animals was determined by inductively coupled plasma mass spectrometry (ICP MS). The other essential elements (Cu, Fe, Mn, P, S, and Zn) were determined by inductively coupled plasma optical emission spectrometry (ICP OES). The content of Ca, K and Mg was determined by atomic absorption spectrometry with flame atomizer (F-AAS). The hypothesis has been that the increased intake of selenium should improve the use of other essential elements by the rat organism. It was expected that there will be influenced elements mainly involved in the defense of the organism against oxidative stress. This was not confirmed by this experiment. Changes in the concentrations of these elements occurred only at very high dose of selenium that is already toxic to the organism. This toxic effect could be also responsible for fifty percent mortality of rats in group E, where perhaps even increased concentration of vitamin E could not sufficiently reduce the toxicity of high doses of selenium.

Introduction: Malgré l'absence d'innervation cholinergique, les vaisseaux sont très réactifs à la présence d'acétylcholine (ACh). De plus, ce neurotransmetteur est couramment utilisé pour évaluer la fonction endothéliale des vaisseaux. Cependant, les informations sur les cholinestérases vasculaires (ChE), les enzymes qui mettent fin à l'action de l'ACh, sont rares. Le principal objectif de cette thèse de doctorat était de caractériser les ChE vasculaires et l'ensemble du système cholinergique de l'aorte dans des conditions normales et pathologiques. Méthodes: Des rats Wistar mâles adultes et des rats spontanément hypertendus (SHR) nourris avec une alimentation régulière ou riche en graisses ont été utilisés dans le cadre du projet. L'expression relative des enzymes et des transporteurs étudiés a été déterminée par la méthode RT-qPCR. Les activités de ChE dans les extraits de tissus ont été mesurées par la méthode d'Ellman, la coloration de l'activité a été réalisée par la méthode de Tsuji et la localisation des protéines a été faite par double immunohistochimie. Les formes moléculaires de ChE ont été séparées par des gradients de saccharose. Résultats et conclusion: Toutes les enzymes et tous les transporteurs impliqués dans la synthèse, le stockage, la libération et la dégradation de l’ACh ont été détectés dans l'aorte du rat au niveau de l'ARNm et au niveau des protéines. Cela confirme que l'aorte est un tissu cholinergique non neuronal, capable de soutenir pleinement le cycle de vie des ACh. Les ChE sont présents principalement sous forme de formes ancrées dans la PRiMA dans chaque partie de l'aorte, tandis que la butyrylcholinestérase (BChE) est l’enzyme dominante, localisée principalement sur le muscle lisse. Dans les rat SHR, des niveaux plus faibles de BChE ont été détectés, accompagnés d'une diminution des expressions relatives de la carnitine acétyltransférase et des transporteurs de cations organiques. Cela suggère une signalisation cholinergique plus faible dans l'aorte de la SHR par rapport aux rats normotendus. Dans l'expérience pharmacologique, l'inhibition du BChE et l'alimentation riche en graisses ont toutes deux entraîné une prise de poids significative et une augmentation des taux sériques de TAG. De plus, un régime riche en graisses a induit une augmentation des niveaux d'ARNm du BChE, indiquant son implication dans le métabolisme des lipides
Introduction: Despite the lack of cholinergic innervation, vessels are highly reactive to the presence of acetylcholine (ACh). Moreover, this neurotransmitter is commonly used to assess the endothelial function of vessels. However, information about vascular cholinesterases (ChE), the enzymes that terminate ACh action, is spares. The main aim of this dissertation thesis was to characterize vascular ChE and overall non-neuronal cholinergic system in the aorta under physiological and pathological conditions. Methods: Adult male Wistar rats and spontaneously hypertensive rats (SHR) were used in the project, fed either with regular or high-fat diet. Relative expression of studied enzymes and transporters were determined by RT-qPCR method. ChE activities in tissue extracts were measured by Ellman's assay, activity staining was performed by Tsuji’s method and proteins localizations were done by dual immunohistochemistry. Molecular forms of ChE were studied by sucrose gradients. Results and conclusion: The enzymes and transporters necessary for ACh synthesis, storage, release, and degradation were detected in the rat aorta at mRNA and at protein levels. This confirms that aorta is a non-neuronal cholinergic tissue, capable to fully support the ACh life cycle. ChE are present mainly as PRiMA-anchored forms in each part of the aorta, while butyrylcholinesterase (BChE) is the dominant ChE, localized primarily in the smooth muscle. In SHR, lower levels of BChE were detected, accompanied by decreased relative expressions of carnitine acetyltransferase and organic cation transporters. This suggests lower cholinergic signaling in SHR aorta as compared to normotensive rats. In the pharmacological experiment, both inhibition of BChE and high-fat diet resulted in significant weight gain and increased serum TAG levels. Moreover, a high-fat diet induced mRNA expression of BChE. Our data suggest BChE involvement in lipid metabolism
Úvod: Napriek absencii cholínergickej inervácie, cievy sú vysoko reaktívne na prítomnosť acetylcholínu (ACh). Okrem toho, práve tento neurotransmiter sa využíva vo fyziologických experimentoch na sledovanie funkčnosti endotelu. Napriek tomu však chýbajú informácie o prítomnosti cholínesteráz (ChE), enzýmov, ktoré ukončujú jeho účinok v cievach. Cieľom tejto dizertačnej práce bola detailne charakterizovať tieto enzýmy a kompletne preštudovať prítomnosť komponentov neneuronálneho cholínergického systému v aorte normotenzných a spontánne hypertenzných potkanov (SHR). Metódy: V experimentoch boli použité 12-týždňové potkany rodu Wistar a SHR, ktoré boli kŕmené buď štandardnou alebo vysoko-tukovou stravou. Relatívna expresia študovaných enzýmov a transportérov bola stanovená metódou RT-qPCR. Aktivity ChE boli stanovené v tkanivových extraktoch pomocou Ellmanovej metódy, aktivitné farbenie bolo prevedené podľa Tsujiho metódy. Na vizualizáciu a lokalizáciu bola využitá metóda dvojfarebnej immunohistochémie. Molekulové formy ChE boli charakterizované pomocou metódy sacharózového gradientu. Výsledky a diskusia: Všetky enzýmy a transportéry, ktoré sú potrebné na syntézu, uchovávanie, vylučovanie a degradáciu ACh boli potvrdené nielen na úrovni mRNA, ale aj na úrovni proteínov. Tieto zistenia potvrdzujú, že aorta patrí medzi neneuronálne cholínergické tkanivá. ChE sú prítomné primárne v PRiMA-kotvenej forme v každej časti aorty, pričom butyrylcholínesteráza (BChE) je dominantná a je prítomná hlavne v hladkom svalstve. V spontánne hypertenznom modeli bola detegovaná nižšia BChE aktivita a tiež nižšia relatívna expresia karnitínacetyltransferázy a organických katiónových transportérov. Vo farmakologickom experimente, aj inhibícia BChE, aj vysoko-tuková strava spôsobila signifikantný prírastok hmotnosti a zvýšenie sérových hladín triacylglycerolov. Okrem toho, vysoko-tuková strava indukovala zvýšenie hladín mRNA pre BChE, čo naznačuje dôležitú úlohu tohto enzýmu nielen vo fyziológii ciev, ale aj v metabolizme lipidov

Both sympathoneural and sympathoadrenal systems are involved in the regulation of arterial blood pressure and in the pathogenesis of hypertension. Spontaneously hypertensive rats (SHR), the mostly used animal model of genetic hypertension, is characterized by multiple molecular, morphological and functional alterations at different levels of sympathoneural and sympathoadrenal systems. The study of young prehypertensive SHR allows to reveal the abnormalities preceding hypertension development, whereas adult SHR with established hypertension offers a better model for the treatment of human essential hypertension. The aim of my PhD Thesis was to describe abnormalities in sympathoneural and sympathoadrenal systems in SHR under different conditions. Firstly, ontogenetic differences which might contribute to hypertension development were determined. Secondly, the effect of chemical sympathectomy induced by guanethidine in adulthood on cardiovascular parameters and on the compensatory mechanisms counteracting the reduction of blood pressure were studied. Thirdly, stress-induced cardiovascular response and stress-induced changes of sympathoneural and sympathoadrenal systems were described in adult SHR. My Thesis brought several important results. The increased adrenal catecholamine content and the...

The goal of this thesis was to discover the influence of adaptation to chronic hypoxia on ischemic tolerance of heart - this experiment was carried out on two different hypertension kinds of laboratory rats. Spontaneously hypertensive rats (SHR) and rats from a conplastic strain SHR/OlaIpcv-mtBN/Crl , whose mitochondrial genome of the SHR strain was replaced with a mitochondrial genome of the normotensive strain Brown Norway, were exposed to continuous normobaric hypoxia (10% O2) for a period of 3 weeks. On the other hand, the control group of rats was kept in normoxia. At the end of the adaptation period, the ischemic tolerance of heart and the mitochondrial aconitase expression were examined. In the case of both hypertensive strains, the chronic hypoxia led to a significant drop in the size of a myocardial infarction and also to a drop in the number of reperfusion arrhythmias. In the case of the SHR strain, the incidence of ischemic arrhythmias decreased. Chronic hypoxia had no impact on the aconitase expression for both analysed strains. This thesis showed that the ischemic tolerance of heart can be enhanced in the case of the SHR strain. On the other hand, the mitochondrial genome of the SHR strain does not seem to play any significant role in protection mechanism. Key words: chronic hypoxia,...

Adaptation to chronic hypoxia provides cardioprotective effects. Molecular mechanism of this phenomenon is not yet completely understood, but it is known that cardiac mitochondria play an essential role in induction of protective effects. The purpose of this diploma thesis is to study effects of continuous normobaric hypoxia (CNH; 10 % O2, 21 days) on spontaneously hypertensive rats (SHR) and conplastic strain that is derived from SHR. These animals have nuclear genome of SHR strain and mitochondrial genome of Brown Norway (BN) strain. Cardiac homogenate was used to measure enzymatic activity of malate dehydrogenase (MDH), citrate synthase (CS), NADH-cytochrome c oxidoreductase, succinate-cytochrome c oxidoreductase and cytochrome oxidase (COX). Using Western blot procedure the protein amount of antioxidant enzymes was measured - manganese superoxide dismutase and copper-zinc superoxide dismutase (MnSOD, Cu/ZnSOD), catalase and chosen subunits of oxidative phosphorylation complexes (Ndufa9, Sdha, Uqcrc2, COX-4, MTCO1, Atp5a1). Under normoxic conditions the conplastic strain has lower amount of complex IV subunit MTCO1 in comparison with SHR. This subunit is encoded by mitochondrial DNA and it is one of the seven protein-coding genes in conplastic strain that differ from SHR. Adaptation to hypoxia causes an...

Diplomová práce Abstract - Iveta Brabcová Abstract Ischemia-reperfusion heart injury is one of the most significant diseases affecting mankind and therefore current research pays more attention to its prevention and knowledge of the possible mechanisms which protect the heart. Adaptation to hypoxia has been known for several decades as a cardioprotective intervention but the main issues of protective mechanisms which are induced by the adaptation are still not completely understood. An important role of mitochondria as the main producers of energy and reactive oxygen species which can play a signalizing role in these mechanisms is confirmed in many studies. For this reason a special conplastic strain SHR/OlaIpcv-mtBN/Crl was created. This strain carries the nuclear genome of spontaneously hypertensive rat (SHR) and the mitochondrial genome of normotensive, highly resistant strain Brown Norway (BN). The aim of this study was to compare the expression of selected gene transcripts in the area of energy metabolism, of genes which are related to mitochondrial biogenesis and signaling and antioxidant systems. Comparing the expression was analyzed between strains and after chronic hypoxia adaptation, which cause cardioprotective phenotype in both of these strains. Our results showed a different expression HIF-1α...

Vascular resistance is mainly determined by the contraction of vascular smooth muscle (VSM), which is regulated by the phosphorylation of myosin light chain (MLC). VSM contraction is initiated by calcium influx into the VSM cells, which is mediated by transient receptor potential (TRP) channels and L-type voltage- dependent calcium channels (L-VDCC). On the other hand, calcium sensitization is a mechanism enhancing vascular contractile response at a given level of intracellular calcium by RhoA/Rho kinase pathway-mediated inhibition of myosin light chain phosphatase. In this thesis I present the data about i) the role of TRP channels in the mechanisms of vascular smooth muscle contraction, ii) enhanced contractility of arteries from spontaneously hypertensive rats (SHR), and iii) the differences in contraction of arteries from normotensive and hypertensive rats related to the role of RhoA/Rho kinase pathway in three types of experimental hypertension (SHR, Ren-2 transgenic rats and salt-sensitive Dahl rats). In the study concerning TRP channels, I compared the effects of three commonly used non-selective TRP channels inhibitors (2-APB, SKF-96365, FFA) on isolated arteries. Among them 2-APB was the most interesting because the observed inhibitory effects of 2-APB were dependent on the type of...

The adrenergic system plays an important role in the regulation of blood pressure. In the spontaneously hypertensive rat, the most studied model of essential hypertension, many components of the adrenergic system are altered. Changes in expression level of any catecholamine biosynthetic enzymes or any adrenergic receptor subtypes could be one of the causes of hypertension development. In this work, the expression of adrenergic system genes was measured in adrenal gland, renal cortex and renal medulla of the spontaneously hypertensive (SHR), Wistar-Kyoto and Brown Norway rats at the age of thirteen weeks. In adrenal gland of SHR, all four catecholamine biosynthetic enzymes (tyrosine hydroxylase, DOPA decarboxylase, dopamine β-hydroxylase and phenylethanolamine-N- methyltransferase) and almost all subtypes of adrenergic receptors (with the exception of Adra1a and Adra1d) were underexpressed. This generally decreased expression in adrenal gland of SHR suggests that at least a part of regulation of adrenergic system gene expression is common. The mechanism of this downregulation in SHR could be a negative feedback through adrenergic receptors stimulated by high plasma noradrenaline concentration. In the kidney of SHR, there were no differences in the expression of most of adrenergic receptor subtypes with the...

The circadian system is an important coordinator of physiological functions of a mammalian organism. It comprises of a central oscillator represented by cells in the suprachiasmatic nuclei of hypothalamus (SCN) and peripheral oscillators in most if not all cells of peripheral tissues. The peripheral oscillators, similarly to the central ones, generate circadian oscillations at the level of so called clock genes and their protein products. In peripheral tissues, oscillations in expression of the individual clock genes are autonomous, however, they need to be synchronized to ensure their robust rhythmic expression. The peripheral clocks are synchronized mainly by rhythmical signals from the SCN, including signals regulating food intake. Disturbances in the clock gene expressions, as well as impaired synchronization signals, can result in various pathophysiological states. Spontaneously hypertensive rat (SHR) strain is a convenient animal model to study potential connection between the disturbed circadian system and progressive development of hypertension and metabolical diseases in mammals. Various studies have shown differences in the rhythmical expression of clock genes between SHR strain and normotensive Wistar/Wistar-Kyoto strain. The aim of this thesis is to provide insight into the early...