However, because real-time PCR does not measure protein synthesis

However, because real-time PCR does not measure protein synthesis, such results must be analyzed together with those obtained Selleckchem Talazoparib in functional experiments. Nevertheless, these data strongly indicate that ET-1, but not its receptors,

is synthesized in lower amounts in the femoral veins of animals subjected to exercise. The reduction of ET-1 production in the femoral vein, if it did in fact occur, may have been due to the exercise-induced elevation of shear stress. It has been reported that ET-1 production may vary depending on the time or the level of shear stress to which the endothelial cells are exposed [14]. According to these authors, higher shear stress levels reduce the release of ET-1 in cultured of human umbilical vein endothelial cells. Similarly, shear stress decreased the ppET-1 mRNA expression in a

time and dose-dependent STA-9090 price manner in both cultured human umbilical vein endothelial cells [27] and in cultured human retinal microvascular endothelial cells [11]. Although it has been extensively studied, the effects of shear stress on the local expression of ET-1 remain controversial. Some studies suggest that high levels of shear stress decrease the production of ET-1 in several cultured endothelial cells, while others show the opposite [41] and [42]. These conflicting data reflect the complexity of the mechanisms that modulate the expression of these genes, wherein the intensity and time of exposure to shear stress are the determining variables. Interestingly, the reduction in ppET-1 Carnitine dehydrogenase mRNA expression in femoral veins reached statistical significance only in animals exposed to physical training at 24 h after the last session. This finding indicates that a reduction in trained animals may be a floating phenomenon and that the peak comes after a rest period. Thus, data extrapolations from a specific vascular bed or from cells in culture to the entire cardiovascular system

must be performed carefully. Moreover, it reinforces the importance of studying the effects of exercise on different portions of the cardiovascular system, including femoral veins. Tissue-specific modifications of ET-1 expression have been previously proposed to be involved in the integrated physiological response during exercise [18], [19] and [20]. Possibly, in vascular beds where exercise elevates blood flow, as in the femoral vein, the reduction of ET-1 expression avoids an uncontrolled increase in flow resistance. However, organ bath experiments demonstrated that in absence of NO, the ETB-mediated release of vasodilator prostanoids appears to maintain reduced Ang II responses in femoral veins taken from exercised animals. Perhaps, though the local ET-1 expression may be reduced, its effects on the endothelial release of prostanoids mediated by ETB may be increased in femoral veins during exercise.

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