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
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
High blood pressure (BP) of L-NAME hypertensive rats is maintained not only by the absence of nitric oxide (NO)-dependent vasodilatation but also by the enhancement of both sympathetic and angiotensin II-dependent vasoconstriction. The aim of the present study was to evaluate the role of inhibitory G (Gi) proteins, which are involv ed in tonic sympathetic vasoconstriction, in the pathogenesis of NO-deficient hypertension. We therefore studied BP response to chronic L-NAME administration (60 mg/kg/day for 4 weeks) in rats in which the in vivo inactivation of Gi proteins was induced by injection of pertussis toxin (PTX, 10 μg/kg i.v.). The impairment of sympathetic vasoconstriction due to PTX-induced Gi protein inactivation prevents the full development of NO-deficient hypertension because BP of PTX-treated rats subjected to chronic L-NAME administration did not reach hypertensive values. Nevertheless, chronic NO synthase inhibition per se is capable to increase moderately BP even in PTX-treated rats. Our data suggest that the sympathetic vasoconstriction is essential for the development of established NO-deficient hypertension., J. Zicha ... [et al.]., and Obsahuje seznam literatury
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