[Non-Central Influences of α2-Adrenergic and Imidazoline Agonist Interactions in Isolated ardiomyocytes Cardiac Cells].

Abstract

AIM\nto investigate the functional interaction of α2-adrenergic and imidazoline receptors recently identified on the sarcolemma of isolated cardiomyocytes for regulation of the intracellular calcium and the production of the signal molecule of nitric oxide (NO).\n\n\nMATERIALS AND METHODS\nexperiments were performed on isolated left ventricular cardiomyocytes of Wistar rats. Potential-dependent Ca2+-currents were measured from the whole-cell by the patch-clamp method in perforated-patch configuration. The intracellular calcium and the production of nitric oxide were estimated from the changes in fluorescence intensity of the Ca2+-specific and NO-sensitive dyes at fluorescent or confocal microscope.\n\n\nRESULTS\nIt has been shown that α2‑adrenergic and imidazoline receptor agonists inhibit L-type Ca2+-currents by themselves, but their effects do not develop against each other s background. The blockade of key effector molecules: protein kinase B (Akt kinase) for α2‑adrenergic receptors, and protein kinase C for imidazoline receptors causes the action of agonists to become additive. Both the selective α2‑agonist, guanabenz, and the specific agonist of the first type imidazoline receptors, rilmenidine, show an additional inhibition of Ca2+-currents against the basal background already reduced by the activation of one of the two receptor systems. Wherein rilmenidine increases the level of free \xa0Ca2+ in the cytosol, and guanabenz, on the contrary, decreases it. The action of guanabenz does not develop against the background of rilmenidine, although it, in turn, effectively increases the intracellular level of calcium in guanabenz-pretreated cardiac cells. Activation of α2‑adrenergic receptors leads to significant stimulation of the endothelial isoform of NO-synthase, and as a result to an increase in the NO level. Activation of imidazoline receptors itself does not affect NO synthesis but it prevents the production of NO induced by α2‑agonists.\n\n\nCONCLUSION\nobtained data make it possible to formulate a number of useful recommendations for clinical practice, and also to clarify the non-central peripheral effects arising from the activation of α2‑adrenergic or imidazoline systems under conditions of endogenous hyperactivation on of the two systems.