The aim of our study was to inve stigate mechanism of action of endothelins 1, 2 and 3 on spontaneous activity, tone and intraluminal pressure of human ureter. Both longitudinal tension and intraluminal pressure were recorded from the isolated segments of proximal human ureter. Endothelins 1, 2 and 3 (5.35x10 -11 M- 5.05x10-8M) produced concentration-dependent tonic contraction and sustained increase in intraluminal pressure of isolated preparations of hum an ureter. Endo thelins 1 and 3 produced also concentration-dependent inhibition of spontaneous, phasic contractions of the isolated preparations. Selective antagonist of ETA receptors BQ123 and selective antagonist of ET B receptors BQ788 produced significant inhibition of endothelin-1-induced tonic contraction (pA2=8.80 and 6.55, respectively) and increase in intraluminal pressure (pA2=8.68 and 7.02, respectively), while they did not affect endothelin-1-induced inhibition of spontaneous activity. Endothelin 1 produces increase in tone and intraluminal pressure of isolated human ureter acting on both ETA and ETB receptors, the first one being functionally more important. On ly endothelins 1 and 3 inhibit spontaneous, phasic activity of human ureter, but this effect was not blocked by selective antagonists of ETA and ETB receptors., S. M. Jankovic ... [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