RESUMO
The present study aimed to establish the role of NO and mechanisms of plaferon LB (PLB) (USA patent N WO 02/12444 A2) effectiveness in the regulation of arterial blood pressure (ABP) during hemorrhagic shock (HS). As it follows from the results of our study and literary data analysis, stress-hormone mediated receptor-induced accumulation of Ca2+ ions in vascular cells occurs during experimental HS. At that, rapid release of large amount of NO due to Ca-dependent eNOS activation in endothelium results in the prevalence of NO-dependent relaxation mechanisms over Ca2+-dependent constriction in smooth muscle cells with subsequent abrupt decrease in ABP. In experimental HS, reproduced against preliminary administration of isoptine, blockage of Ca entry in endothelial cells prevents intensification of Ca-dependent synthesis of nitric oxide, and consequently, prevents activation of NO-dependent mechanisms of dilatation thereby facilitating ABP elevation. Preliminary administration of LNAME inhibits nitric oxide synthesis in blood vessel endothelium and consequently prevents activation of NO-dependent mechanisms of dilatation. Insignificant (by 17%) increase of Ca2+ levels in artery of animals of this experimental group is likely due to transitory hormone-induced entry of calcium through slow Ca channels, which at the inhibition of NO-dependent vasodilatation provides constriction of blood vessels and normalization of ABP. Given the ability of PLB to regulate nitric oxide synthesis at various pathological processes, we suggest that normalization of ABP by this preparation during HS is mainly due to NO-modulating activity of PLB. PLB maintains physiological concentrations of NO in blood vessels. Nitric oxide, in its turn, provides normalization of ABP in experimental animals due to the regulation of vascular smooth muscle tone through the modulation of Ca2+ levels. Thus, we can conclude that nitric oxide plays significant role in the regulation of the balance between constrictory and dilatatory mechanisms of vascular tone. PLB due to its NO modulating activity provides maintenance of physiological activity of nitric oxide, normalization of Ca2+ levels and ABP in blood vessels.
