Hereditary hypertriglyceridemic (hHTG) rats are characterized by increased blood pressure and impaired endotheliumdependent relaxation of conduit arteries. The aim of this study was to investigate the effect of long-term (4 weeks) treatment of hHTG rats with three drugs which, according to their mechanism of action, may be able to modify the endothelial function: simvastatin (an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase), spironolactone (an antagonist of aldosterone receptors) and L-arginine (a precursor of nitric oxide formation). At the end of 4th week the systolic blood pressure in the control hHTG group was 148±2 mm Hg and in control normotensive Wistar group 117±3 mm Hg. L-arginine failed to reduce blood pressure, but simvastatin (118±1 mm Hg) and spironolactone (124±4 mm Hg) treatment significantly decreased the systolic blood pressure. In isolated phenylephrine-precontracted aortic rings from hHTG rats endothelium-dependent relaxation was diminished as compared to control Wistar rats. Of the three drugs used, only simvastatin improved acetylcholine-induced relaxation of the aorta. We conclude that both simvastatin and spironolactone reduced blood pressure but only simvastatin significantly improved endothelial dysfunction of aorta. Prominent increase in the expression of eNOS in large conduit arteries may be the pathophysiological mechanism underlying the protective effect of simvastatin in hHTG rats., J. Török, I. L'upták, J. Matúšková, O. Pecháňová, J. Zicha, J. Kuneš, F. Šimko., and Obsahuje bibliografii
Although exposure to continuous light is associated with hypertension and modulates the outcome of ischemiareperfusion injury, less attention has been paid to its effects on cardiac morphology. We investigated whether 4-week exposure of experimental rats to continuous 24 h/day light can modify cardiac morphology, with focus on heart weight, fibrosis and collagen I/III ratio in correlation with NO-synthase expression. Two groups of male adult Wistar rats were studied: controls exposed to normal light/dark cycle (12 h/day light, 12 h/day dark) and rats exposed to continuous light. After 4 weeks of treatment the absolute and the relative heart weights were determined and myocardial fibrosis and collagen type I/III ratio were evaluated using picrosirius red staining. Endothelial and inducible NO-synthase expression was detected immunohistochemically. The exposure of rats to continuous light resulted in an increase of body weight with proportionally increased heart weight. Myocardial fibrosis remained unaffected but collagen I/III ratio increased. Neither endothelial nor inducible NO-synthase expression was altered in light-exposed rats. We conclude that the loss of structural homogeneity of the myocardium in favor of collagen type I might increase myocardial stiffness and contribute to functional alterations after continuous light exposure., L'. Paulis, R. Važan, F. Šimko, O. Pecháňová, J. Styk, P. Babál, P. Janega., and Obsahuje bibliografii
Aldosterone receptor antagonist, spironolactone, has been shown to prevent remodeling of the heart in several models of left ventricular hypertrophy. The aim of the present study was to determine whether the treatment with spironolactone can prevent hypertension, reduction of tissue nitric oxide synthase activity and left ventricular (LV) and aortic remodeling in NG-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. Four groups of rats were investigated: control, spironolactone (200 mg/kg), L-NAME (40 mg/kg) and L-NAME + spironolactone (in corresponding dosage). Animals were studied after 5 weeks of treatment. The decrease of NO-synthase activity in the LV and kidney was associated with the development of hypertension and LV hypertrophy, with increased DNA concentration in the LV, and remodeling of the aorta in the L-NAME group. Spironolactone prevented the inhibition of NO-synthase activity in the LV and kidney and partially attenuated hypertension and LVH development and the increase in DNA concentration. However, remodeling of the aorta was not prevented by spironolactone treatment. We conclude that the aldosterone receptor antagonist spironolactone improved nitric oxide production and partially prevented hypertension and LVH development without preventing hypertrophy of the aorta in NO-deficient hypertension. The reactive growth of the heart and aorta seems to be controlled by different mechanisms in L-NAMEinduced hypertension., F. Šimko, J. Matúšková, I. L'upták, T. Pinčíková, K. Krajčírovičová, S. Štvrtina, J. Pomšár, V. Pelouch, L'. Paulis, O. Pecháňová., and Obsahuje bibliografii
NG-nitro-L-arginine-methyl ester (L-NAME)-induced hypertension is associated with protein remodeling of the left ventricle. The aim of the study was to show, whether aldosterone receptor blocker spironolactone and precursor of NOproduction L-arginine were able to reverse the protein rebuilding of the left ventricle. Six groups of male Wistar rats were investigated: control 4 (4 weeks placebo), L-NAME (4 weeks L-NAME), spontaneous-regression (4 weeks L-NAME + 3 weeks placebo), spironolactone-regression (4 weeks L-NAME + 3 weeks spironolactone), L-arginineregression (4 weeks L-NAME + 3 weeks arginine), control 7 (7 weeks placebo). L-NAME administration induced hypertension, hypertrophy of the left ventricle (LV), and the increase of metabolic and contractile as well as soluble and insoluble collagenous protein concentration. The systolic blood pressure and relative weight of the LV decreased in all three groups with regression, while the most prominent attenuation of the LVH was observed after spironolactone treatment. In the spontaneous-regression and L-arginine-regression groups the concentrations of individual proteins were not significantly different from the control value. However, in the spironolactone-regression group the concentration of metabolic, contractile and insoluble collagenous proteins remained significantly increased in comparison with the control group. The persistence of the increased protein concentration in the spironolactone group may be related to the more prominent reduction of myocardial water content by spironolactone., F. Šimko, A. Potáčová, V. Pelouch, L'. Paulis, J. Matúšková, K. Krajčírovičová, O. Pecháňová, M. Adamcová., and Obsahuje bibliografii
Factors modulating cardiac susceptibility to ischemia-reperfusion (I/R) are permannetly attracting the attention of experimental cardiology research. We investigated, whether continuous 24 h/day light exposure of rats can modify cardiac response to I/R, NO-synthase (NOS) activity and the level of oxidative load represented by conjugated dienes (CD) concentration. Two groups of male adult Wistar rats were studied: controls exposed to normal light/dark cycle (12 h/day light, 12 h/day dark) and rats exposed to continuous light for 4 weeks. Perfused isolated hearts (Langendorff technique) were exposed to 25 min global ischemia and subsequent 30 min reperfusion. The recovery of functional parameters (coronary flow, left ventricular developed pressure, contractility and relaxation index) during reperfusion as well as the incidence, severity and duration of arrhythmias during first 10 min of reperfusion were determined. The hearts from rats exposed to continuous light showed more rapid recovery of functional parameters but higher incidence, duration and severity of reperfusion arrhythmias compared to controls. In the left ventricle, the NOS activity was attenuated, but the CD concentration was not significantly changed. We conclude that the exposure of rats to continuous light modified cardiac response to I/R. This effect could be at least partially mediated by attenuated NO production., R. Važan, P. Janega, S. Hojná, J. Zicha, F. Šimko, O. Pecháňová, J. Styk, L'. Paulis., and Obsahuje bibliografii
Endothelial dysfunction may be considered as the interstage between risk factors and cardiovascular pathology. An imbalance between the production of vasorelaxing and vasoconstricting factors plays a decisive role in the development of hypertension, atherosclerosis and target organ damage. Except vasorelaxing and antiproliferative properties per se, nitric oxide participates in antagonizing vasoconstrictive and growth promoting effects of angiotensin II, endothelins and reactive oxygen species. Angiotensin II is a potent activator of NAD(P)H oxidase contributing to the production of reactive oxygen species. Numerous signaling pathways activated in response to angiotensin II and endothelin-1 are mediated through the increased level of oxidative stress, which seems to be in casual relation to a number of cardiovascular disturbances including hypertension. With respect to the oxidative stress, the NO molecule seems to be of ambivalent nature. On the one hand, NO is able to reduce generation of reactive oxygen species by inhibiting association of NAD(P)H oxidase subunits. On the other hand, when excessively produced, NO reacts with superoxides resulting in the formation of peroxynitrite, which is a free radical deteriorating endothelial function. The balance between vasorelaxing and vasoconstricting substances appears to be the principal issue for the physiological functioning of the vascular bed., O. Pecháňová, F. Šimko., and Obsahuje bibliografii