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Biomedical subjects

J Kyselovic

Publications and source records attributed to J Kyselovic.

At least 19 recordsLinked to original sources
PubMed2006

Protective effect of selected flavonoids on in vitro daunorubicin-induced cardiotoxicity.

Flavonoids are an ubiquitous group of polyphenolic substances with varied chemical structures present in foods of plant origin and act as free radical scavenging and chelating agents with a variety of biological activities. Using a model of spontaneously beating, cultured adult rat cardiomyocytes, this study examined the cardioprotective role of quercetin, naringenin, pycnogenol and a model antioxidant, trolox, against daunorubicin-induced toxicity. Cardiomyocyte protection was assessed by MTT test and extracellular lactate dehydrogenase detection. Protection of cardiomyocytes was concentration/dose dependent for quercetin > naringenin > pycnogenol > trolox. Quercetin (10(-4)-10(-6) mol/L) after 24 h of co-incubation with daunorubicin significantly increased the cardiomyocyte survival in all tested concentrations (p < 0.001). The cytoprotective effect of naringenin (10(-4)-10(-6) mol/L) was similar to those of quercetin (p < 0.001 and p < 0.01, respectively). Pycnogenol was the least effective of the flavonoids studied. On the other hand, all tested flavonoids had significantly better protective effects than trolox. The leakage of lactate dehydrogenase induced by daunorubicin was also prevented by the studied compounds and was in accordance with their cytoprotective activity.

Animals↗
PubMed2004

[The contribution of 24-hour ambulatory blood pressure monitoring to the treatment of hypertensive patients in teaching hospital in Nitra].

BACKGROUND: Twenty-four hours ambulatory blood pressure monitoring (ABPM) in patients with arterial hypertension is a recognized method for diagnostic of hypertension and for monitoring of the effects of antihypertensive treatment. The aim of our study was to evaluate the contribution of ABPM in clinical practise. METHODS AND RESULTS: Records of ABPM in hypertensive patients were evaluated retrospectively. Total of 37 patients aged 27-69 years with the newly diagnosed hypertension in the period of 1996-2001 were included in the study. The indications to ABPM, percent of dippers and no dippers diagnosed on the basis of diurnal index and the modification in antihypertensive treatment in no dippers were analysed. 1) ABPM was used for monitoring of the effect of antihypertensive therapy in 78%, for diagnosing borderline hypertension in 19% and of white coat hypertension in 3% cases; 2) 22 patients (59%) were diagnosed as no dippers; 3) Antihypertensive therapy was modified in 7 patients no dippers (20%). CONCLUSIONS: The contribution of ABPM is obvious, however at current conditions its broader application could increase the diagnostic and therapeutical quality of clinical decision making in hypertensive patients.

Adult↗
PubMed2003

[Caveolar functions and caveolin structural proteins].

Caveolae are small invaginations of the plasma membrane found in a variety of cells. The major components of caveolae are cholesterol, sfingolipids and structural proteins named caveolins. Three caveolin isoforms are known: caveolin-1, caveolin-2 and caveolin-3. Adipocytes, endothelial cells, pneumocytes and fibroblasts express caevolin-1 and-2, whereas caveolin-3 expression is limited to muscle cells types. Caveolae and caveolins have diverse functions including vesicular transport, cholesterol homeostasis, signal transduction or tumor suppression. The aim of the present review is to explain what is known about caveolae and caveolins.

Caveolae↗
PubMed2002

Captopril fails to reverse hypertrophy of the left ventricle induced by aortic insufficiency in rabbits.

Angiotensin converting enzyme (ACE) inhibition has been reported to induce regression of hypertrophy in several models of hemodynamic pressure overload. The aim of the present study was to determine whether the ACE inhibitor captopril can reduce hypertrophy of the left ventricle induced by a chronic volume overload and modify collagen composition of the hypertrophied myocardium. Rabbits with four months lasting aortic insufficiency were divided into two groups: treated with captopril (20 mg/kg/day) for five weeks and treated with placebo. The respective control groups were represented by sham-operated animals. Aortic insufficiency induced a decrease of diastolic pressure, an increase of systolic and pulse pressure, hypertrophy of the left and right ventricle, and an increase of hydroxyproline content in the left ventricle without a change of hydroxyproline concentrations in either ventricle. Captopril treatment further enhanced pulse pressure by decreasing diastolic blood pressure. Hypertrophy of the left ventricle, hydroxyproline content and concentration in both ventricles were unaffected by captopril treatment. It is concluded that ACE inhibition did not reverse the left ventricular hypertrophy developed as a result of overload induced by aortic insufficiency. We suggest that mechanisms different from activation of the renin-angiotensin system may play a decisive role in the maintenance of hypertrophy in this particular model of volume hemodynamic overload.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Effects of amlodipine and lacidipine on cardiac remodelling and renin production in salt-loaded stroke-prone hypertensive rats.

1. Calcium channel blockers (CCBs) are anti-hypertensive drugs that are usually considered to act mainly as vasodilators. We investigated the relation between the reduction of blood pressure evoked by two long-acting CCBs and their protective effect against cardiac and renal damage in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). 2. SHRSP were exposed to high dietary salt intake (1% NaCl in drinking solution) from 8 to 14 weeks of age, with or without amlodipine or lacidipine at three dosage regimens producing similar effects on blood pressure. 3. The lowest dosages of both drugs had non-significant effects on blood pressure but inhibited the paradoxical increases in plasma renin activity (PRA) and in renin mRNA in kidney that were found in salt-loaded SHRSP. The lowest dosage of lacidipine (but not of amlodipine) restored the physiological downregulation of renin production by high salt and reduced left ventricular hypertrophy and mRNA levels of atrial natriuretic factor and transforming growth factor-beta1. 4. The intermediate dosages reduced blood pressure and PRA in a comparable manner, but cardiac hypertrophy was more reduced by lacidipine than by amlodipine. 5. Although the highest doses exhibited a further action on blood pressure, they had no additional effect on cardiac hypertrophy, and they increased PRA and kidney levels of renin mRNA even more than in the absence of drug treatment. 6. We conclude that reduction of blood pressure is not the sole mechanism involved in the prevention of cardiac remodelling by CCBs, and that protection against kidney damage and excessive renin production by low and intermediate dosages of these drugs contributes to their beneficial cardiovascular effects.

Actins↗
PubMed2001

Electrocardiographic diagnosis of left ventricular hypertrophy: is the method obsolete or should the hypothesis be reconsidered?

The current ECG diagnosis of LVH is based on QRS voltage criteria and aims to estimate left ventricular mass. Its underlying hypothesis includes unstated assumptions about the non-spatial determinants of QRS voltage;that the electrical properties of hypertrophied myocardium do not differ from those healthy myocardium, and that they are not changed in the course of developing LVH. Since these two assumptions are not true, the performance of the voltage criteria is limited and is reflected in the high number of so-called false negative ECG results, as well as their low sensitivity. The reconsidered hypothesis is based on a more complex understanding of LVH and on the analysis of information provided by electrocardiography. It considers false negative results for LVH diagnosis as a relative voltage deficit, and introduces a new parameter for its quantification: the specific potential (the relative QRS voltage).The relative voltage deficit is related to changes of active and passive electrical properties (electrophysiological remodelling) of the hypertrophied myocardium. This new hypothesis also takes into account changes of the relative QRS voltage in different stages of LVH. The potential of this concept is its usefulness as a parameter in the frame of diagnostics of LVH, of diffuse changes of myocardium, in cardiovascular risk assessment, and well as for evaluation of the effects of therapy.

Electrocardiography↗
PubMed2001

Lacidipine prevents endothelial dysfunction in salt-loaded stroke-prone hypertensive rats.

Endothelium-dependent vasorelaxation is defective in hypertensive rats, especially in conduit arteries. In the stroke-prone spontaneously hypertensive rat, impaired endothelium-dependent vasorelaxation appears to contribute to the pathogenesis of stroke independent of blood pressure. Because treatment with lacidipine, a long-acting calcium channel blocker, protects against stroke and cardiovascular remodeling in this model, we investigated the effect of this treatment on endothelium-dependent vasorelaxation in the aorta. Stroke-prone rats were exposed to a salt-rich diet (1% NaCl in drinking water) with or without lacidipine (1 mg. kg(-1). d(-1)) for 6 weeks. A high-sodium diet (1) increased systolic blood pressure, aortic weight, and wall thickness and plasma renin activity (P<0.05); (2) markedly reduced nitric oxide (NO)-mediated, endothelium-dependent relaxation of aortic rings to acetylcholine and the sensitivity to the relaxing effect of S-nitroso-N-acetylpenicillamine, an NO donor (P<0.001); and (3) induced an elevation of preproendothelin-1 mRNA levels in aortic tissue (P<0.01) without affecting endothelial NO synthase mRNA levels. Lacidipine treatment prevented the salt-dependent functional and structural alterations of the aorta, including the overexpression of the preproendothelin-1 gene, and increased endothelial NO synthase mRNA levels in aortic tissue (P<0.01). In conclusion, lacidipine protects stroke-prone hypertensive rats against the impairment of endothelium-dependent vasorelaxation evoked by a salt-rich diet, and this effect may contribute to its beneficial effect against end-organ damage and stroke.

Animals↗
PubMed2001

[Role of orthogonal electrocardiography and vectorcardiography in a paradigm shift in diagnosis of left ventricular hypertrophy].

A new contingency approach to the ECG diagnostics of left ventricular hypertrophy, its theoretical background, and first results of experimental and clinical studies are presented. This approach considers false negative ECG results as a consequence of the relative voltage deficit and introduces a new parameter: the specific potential of myocardium. As well it considers nonlinear changes of non-spatial determinants with respect to the stage and progression of left ventricular hypertrophy. The potential advantages of the concept of the specific potential of myocardium can be summarized as follows: (1) It utilizes equally both electrocardiographic and echocardiographic information, without stressing the priority or neglecting any of particular methods and creates a broader basis for the clinical diagnosis of left ventricular hypertrophy, (2) It utilizes also the false negative ECG results for diagnostics and quantifies the relative voltage deficit.

Electrocardiography↗
PubMed2000

[Effects of a (fluorophenyl) piperazine derivative (substance IIIv) on cardiovascular function].

The present paper links up with the study of principal pharmacological effects of newly synthesized aryloxyaminopropanols substituted with 1,4-piperazine derivatives in the hydrophilic moiety of the molecule. The substance with the working name IIIv showing the highest beta-adrenolytical and vasodilating effect underwent further pharmacological evaluations with the aim of contributing to the elucidation of the mechanism of its action. After 7-day administration of the substance in two doses (5 and 50 mg.kg-1), the changes in the reactibility of arterial preparations were investigated on three models of the contraction of the isolated rat aorta (KCl, noradrenaline, and PGF2 alpha) from both qualitative and quantitative views. The results were also supplemented with organometric studies of the effect of the substance in rats.

Adrenergic beta-Antagonists↗
PubMed1999

Captopril increased mitochondrial coenzyme Q10 level, improved respiratory chain function and energy production in the left ventricle in rabbits with smoke mitochondrial cardiomyopathy.

The aim of the study was to show whether the ACE inhibitor captopril is able to protect the heart against the deleterious effect of passive cigarette smoking on left ventricular mitochondria. Four groups of rabbits were investigated: control (C), passive smoking of three cigarettes twice daily/30 minutes (S), control + captopril (7.5 mg/kg body weight twice daily) (Cap), and smoking + captopril (SCap) as in group 2 and 3. Three weeks lasting passive smoking impaired oxidative phosphorylation, diminished cytochrome oxidase activity and increased the mitochondrial F1-ATPase protein concentration. Moreover, the level of coenzyme Q10 (CoQ10) and coenzyme Q9 were decreased. Simultaneous treatment with captopril prevented partly the decrease of CoQ10 level, deterioration of oxidative phosphorylation, diminution of cytochrome oxidase activity and enhancement of F1-ATPase level. We conclude that captopril protected the myocardium against the harmful effect of passive smoking in rabbits.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Carvedilol and lacidipine prevent cardiac hypertrophy and endothelin-1 gene overexpression after aortic banding.

Carvedilol and lacidipine have been shown to exert cardioprotective effects in rat models of chronic hypertension. We investigated their effects in an acute model of pressure overload produced by suprarenal aortic constriction, in which enhanced myocardial production of endothelin-1 could play a crucial role. In the absence of drug treatment, after 1 week, aortic banding provoked an increase in carotid pressure associated with left ventricular hypertrophy (29%; P<0.01). These changes were accompanied by increased myocardial expression of preproendothelin-1 (2.5 times; P<0.05) and skeletal alpha-actin (3.6 times; P<0.05), but the expression of cardiac alpha-actin was not modified. Oral administration of carvedilol at a dose of 30 mg. kg(-1). d(-1) to rats with aortic banding normalized carotid pressure and left ventricular weight as well as preproendothelin-1 and skeletal alpha-actin gene expression. Carvedilol at a lower dose (7.5 mg x kg(-1) x d(-1)) and lacidipine 1 mg x kg(-1) x d(-1) had only moderate and nonsignificant effects on carotid pressure but largely prevented left ventricular hypertrophy (P<0.01) and preproendothelin-1 overexpression (P<0.05). Labetalol (60 mg x kg(-1) x d(-1)) tended to exert similar effects but insignificantly. These results show that the antihypertrophic properties of carvedilol and lacidipine are partly independent of their antihypertensive effects and may be related to their ability to blunt myocardial preproendothelin-1 overexpression. Moreover, carvedilol at a dose of 7.5 mg x kg(-1) x d(-1) did not prevent myocardial overexpression of skeletal alpha-actin, which suggests that, in this model, reexpression of a fetal gene can be activated by pressure overload independently of cardiac hypertrophy.

Actins↗
PubMed1998

Prevention of salt-dependent cardiac remodeling and enhanced gene expression in stroke-prone hypertensive rats by the long-acting calcium channel blocker lacidipine.

OBJECTIVE: To analyze the effect of the long-acting calcium channel blocker lacidipine on cardiovascular remodeling induced by salt loading in a genetic model of hypertension. DESIGN: We examined the influence of threshold doses of lacidipine, with little blood-pressure lowering effect, on cardiac weight and gene expression in stroke-prone spontaneously hypertensive rats (SHRSP). METHODS: SHRSPs (8-week-old) were randomly allocated to four groups: control, salt-loaded SHRSP and salt-loaded SHRSP treated with lacidipine at 0.3 and 1 mg/kg per day. Systolic blood pressure was measured by the tail-cuff method. At the end of 6 weeks of treatment, ventricles were collected and weighed. Ventricular messenger RNA was extracted and subjected to Northern blot analysis. RESULTS: Lacidipine (0.3 mg/kg per day) not only prevented the salt-dependent cardiac hypertrophy and the slight increase in systolic blood pressure induced by salt, but also prevented, largely or completely, salt-dependent increases in ventricular levels of several gene products: skeletal and cardiac alpha-actin, beta-myosin heavy chain (beta-MHC), type I collagen, long-lasting (L)-type calcium channel and preproendothelin-1. At a higher dose of 1 mg/kg per day, lacidipine further decreased systolic blood pressure below the level of control SHRSP, completely prevented salt-dependent overexpression of the beta-MHC gene and markedly attenuated salt-dependent overexpression of the transforming growth factor-beta1 gene. CONCLUSIONS: Lacidipine prevents the cardiac remodeling and enhanced gene expression induced by salt loading in SHRSP at doses that only minimally affect the high systolic blood pressure.

Animals↗
PubMed1997

Structural changes in the aorta of the hereditary hypertriglyceridemic rat.

Structural changes in the ascending thoracic aorta of hereditary hypertriglyceridemic (hHTG), insulin-resistant, and hypertensive rats were studied using transmission electron microscopy. Normotensive Wistar rats were used as controls. The most-pronounced morphological changes were observed in the tunica intima. Endothelial cells of hHTG rats formed a continual layer around the whole circumference. Subendothelial space was enlarged. Some endothelial cells were delaminated from the subendothelial space by big lipid droplets that were often present in the subendothelial space, and the endothelial cells bulged out towards the lumen. Big electron-lucent lipid droplets were present in the majority of the endothelial cells and occupied the main part of the cytoplasm. Degenerative microvesicular and membranous material was present in the cytoplasm. Increased numbers of vesicles of Golgi apparatus and cisternae of endoplasmic reticulum were found. Similar morphological alterations, but in less-extended form, were observed in smooth muscle cells. The organization and orientation of smooth muscle cells were essentially intact. In muscle cells, lipid droplets were localized in close relation to Golgi complex and in dilated cisternae of the sarcoplasmic reticulum. Lipid droplets, degenerative material, myelin figures, myelinoid membranes, and vesicular components were also sporadically found in the intercellular space among muscle cells. This pilot morphological investigation provides further arguments for a thorough and more-focused electron microscopy study of conductance arteries of the hHTG rats.

Animals↗
PubMed1995

Regulation of dihydropyridine and ryanodine receptor gene expression in skeletal muscle. Role of nerve, protein kinase C, and cAMP pathways.

The dihydropyridine (DHP) and ryanodine (RY) receptors play a critical role in depolarization-induced calcium release in skeletal muscle, yet the factors which govern their expression remain unknown. We investigated the roles of electrical activity and trophic factors in the regulation of the genes encoding the alpha 1, alpha 2, and beta subunits of the DHP receptor as well as the RY receptor in rat skeletal muscle in vivo. Muscle paralysis, induced by denervation, had no effect on the DHP receptor mRNA levels while the RY receptor mRNA was decreased. In contrast, chronic superfusion of tetrodotoxin onto the sciatic nerve resulted in a marked increase in mRNA levels and transcriptional activity of both DHP and RY receptor genes. Since nerve can induce changes in second messenger pathways which modulate muscle gene expression, we attempted to identify factors which regulate DHP and RY receptor expression using cultured myotubes. Elevated cAMP levels specifically inhibited the expression of RY receptor mRNA while 12-O-tetradecanoylphorbol-13-acetate, an activator of protein kinase C, increased the transcripts encoding the RY receptor and the alpha 1 subunit of the DHP receptor. Changes in the level of mRNAs were paralleled by altered receptor numbers. Neither cAMP nor protein kinase C altered transcriptional activity of the DHP and RY receptor genes. These results demonstrate that neural factor(s) regulate DHP and RY receptor mRNA levels in vivo via transcriptional mechanisms while protein kinase C and cAMP can modulate DHP and RY receptor transcript levels by a transcription-independent process.

Alkaloids↗