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
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