We studied the effect of thiazide-like diuretic – indapamide on fibrosis development in the left ventricle of young spontaneously hypertensive rats (SHR) and assessed the involvement of nitric oxide in this process. Six-week-old male SHR were treated with indapamide (1 mg/kg/day) for six weeks. Age-matched SHR were used as hypertensive and Wistar-Kyoto rats (WKY) as normotensive control. Systolic blood pressure was measured by tail-cuff plethysmography. Nitric oxide synthase (NOS) activity, protein expressions of endothelial (eNOS) and inducible NOS (iNOS), myocardial fibrosis and collagen type I and III were determined in the left ventricle. Indapamide treatment partially prevented SBP increase in SHR (SHR+Indapamide: 157±4, SHR: 171±3, WKY: 119±3 mmHg). Indapamide prevented myocardial fibrosis development in SHR, but without affecting collagen type I to type III ratio. Indapamide did not affect NOS activity as well as eNOS and iNOS protein expressions in the left ventricles evaluated by both Western blot and immunohistochemically. In conclusion, our results indicate that indapamide-induced prevention of myocardial fibrosis is not mediated by nitric oxide-related mechanism., P. Janega, S. Kojšová, L. Jendeková, P. Babál, O. Pecháňová., and Obsahuje bibliografii a bibliografické odkazy
NG-nitro-D-arginine-methyl ester (D-NAME) is considered to be an inactive enantiomer of L-NAME and is generally used as the negative control for NO synthase inhibition with L-NAME. With the aim to compare the effects of 4-week L-NAME and D-NAME treatments on hemodynamic and cardiovascular structural parameters, four groups of male Wistar rats were investigated: the controls and groups administered 40 and 20 mg/kg/day of L-NAME and 40 mg/kg/day of D-NAME. At the end of the experiment, myocardial NO synthase activity decreased by 42, 24 and 25 %; aortic NO synthase activity decreased by 35, 15 and 13 % vs. controls in the L-NAME 40, L-NAME 20 and D-NAME 40 groups, respectively. The DNA concentrations in the myocardium and the aorta increased significantly after L-NAME and D-NAME treatments. The inhibition of NO synthase was accompanied by a significant elevation in systolic blood pressure in all three groups. The LVW/BW ratio increased by 27, 14 and 13 % vs. controls in the L-NAME 40, L-NAME 20 and D-NAME 40 groups, respectively. The aortic wall mass, measured as the crossectional area, increased by 45, 17 and 25 % vs. controls in the L-NAME 40, L-NAME 20 and D-NAME 40 groups, respectively. Myocardial fibrosis represented 0.94 % in the controls, but 7.96, 4.70 and 5.25 % in L-NAME 40, L-NAME 20 and D-NAME 40 groups, respectively. It is concluded that D-NAME, although less affective than L-NAME, inhibits NO synthase activity resulting in hemodynamic and structural changes in the cardiovascular system similar to the changes induced by half the dose of L-NAME. Thus, the consideration of D-NAME as an inactive enantiomer and its use as the negative control needs to be reevaluated., P. Babál, O. Pecháňová, I. Bernátová., 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
Increased amount of collagen type I and decreased amount of type III is described in various pathological processes in the vascular wall. Polyphenols were shown to have protective effect on endothelium, decrease blood pressure and prevent oxidative damage induced by various stimuli. Tetrachlormethane (CCl4) is a toxic substance with known negative systemic effects induced by free radicals. Chronic administration of CCl4 for 12 weeks led to an increase of collagen type I and a decrease of type III in the wall of aorta. Parallel administration of red wine polyphenols significantly reduced the increase of collagen type I, at the same time the content of type III rose to the level above controls. After 4 weeks of spontaneous recovery no changes were observed. If polyphenols were administered during the recovery period, there was a decrease of type I and an increase of type III collagen content in the aorta. It can be concluded that polyphenols have a tendency to lower the amount of type I and to increase the proportion of type III collagen in the wall of the aorta. These changes are significant in prevention or in regression of changes induced by chronic oxidative stress. This effect of polyphenols is most likely the result of their influence on MMP-1 and TIMP activities through which they positively influence the collagen types I and III content ratio in the vascular wall in favor of the type III collagen., L. Hlavačková ... [et al.]., and Obsahuje seznam literatury
The aim of this study was to an alyze the effect of indapamide and its combination with ACE inhi bitor (captopril) and antioxidant (ProvinolsTM) on both myocardial hypert rophy and fibrosis. Wistar rats were treated with L-NAME (40 mg/kg/day, L); L-NAME plus indapamide (1 mg/kg/day), or captopril (10 mg/kg/day), or ProvinolsTM (40 mg/kg/day), or combination of indapamide with captopril, and indapamide with Provinols TM for 7 weeks. Blood pressure (BP), LV hypertrophy an d fibrosis were determined. The content of collagens type I and III was evaluated morphometrically after picrosirius red staining. L-NAME treatment led to increased BP, LV hypertroph y, total fibrosis and relative content of collagens without th e change in collagen type I/III ratio. Indapamide and captopri l decreased BP, LV hypertrophy and the collagen ratio without affecting total fibrosis, while ProvinolsTM reduced BP, the collagen ratio and fibrosis without affecting LV hypertrophy. The combinations decreased all the parameters. Decrease of LV hypertrophy was achieved by drugs with the best reducing effect on BP, fibrosis reduction was reached by the antioxidant treatment with only partial effect on BP. Thus, the combination of an tihypertensive and antioxidant treatment may represent a powerful tool in preventing myocardial remodeling induced by hypertension., L. Hlavačková ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy