Left ventricular hypertrophy (LVH) is the result of interaction between a chronic hemodynamic overload and non-hemodynamic factors. There are several lines of evidence presented in this work suggesting that nitric oxide (NO) may participate in the hypertrophic growth of the myocardium. First, endothelial NO production was shown to be decreased in several types of hemodynamically overloaded circulation both in animals and humans. Second, compounds stimulating NO production were able to diminish the extent or modify the nature of LVH in some models of myocardial hypertrophic growth. Third, arterial hypertension can be induced by inhibition of nitric oxide synthase activity. This NO-deficient hypertension is associated with the development of concentric LVH, myocardial fibrosis and protein remodeling of the left ventricle. The mechanism of LVH development in NO-deficient hypertension is complex and involves decreased NO production and increased activation of the renin-angiotensin-aldosterone system. Cardiovascular protection via ACE inhibition in NO-deficient hypertension may be induced by mechanisms not involving an improvement of NO production. In conclusion, the hypertrophic growth of the LV appears to be the result of interaction of vasoconstrictive and growth stimulating effects of angiotensin II on the one hand and of vasodilating and antiproliferative effects of nitric oxide on the other., F. Šimko, J. Šimko., and Obsahuje bibliografii
Certain liver metabolic diseases point to the presence of disturbances in glycogen deposition. Epinephrine raises the cAMP level that activates protein kinase A leading to the activation of phosphorylase and glycogen breakdown. In the present report, we sought to investigate whether NO is produced during adrenoceptor agonist-induced glycogenolysis in rat hepatocytes in cultures. Isolated glycogen rich rat hepatocytes in cultures were used. NO production (NO2-) was assessed under the effect of adrenergic agonists and adrenergic agonist/antagonist pairs, dibutyryl cyclic AMP sodium-potassium salt (db-cAMP), NO synthase (NOS) inhibitors Nω-nitro-L-arginine methyl ester (L-NAME), aminoguanidine (AG) and the NO donor S-nitroso-N-acetyl penicillamine (SNAP) . The inducible NO synthase (iNOS) mRNA was examined by the reverse transcription-polymerase chain reaction (RT-PCR). Glycogenolysis was quantified by glucose levels released into medium. The amount of glucose and NO2- released by hepatocytes was increased as a result of epinephrine, phenylephrine or db-cAMP treatments. The increase in glucose and NO2- released by epinephrine or phenylephrine was blocked or reduced by prazosin pretreatment and by NOS inhibitors aminoguanidine and L-NAME. iNOS gene expression was up-regulated by epinephrine. It can be concluded that glycogenolysis occurs through α adrenoceptor stimulation and a signaling cascade may involve NO production., J. Hodis, N. Kutinová-Canová, P. Potměšil, L. Kameníková, E. Kmoníčková, Z. Zídek, H. Farghali., and Obsahuje biblografii 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