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Upregulation of α2-adrenoceptor synthesis in SHR cardiomyocytes: Recompense without sense - Increased amounts, impaired commands.

Abstract：

AIMS:to investigate α2-AR subtype distribution and the relationship between receptor amounts and their functionality in normotensive and spontaneously hypertensive rats. METHODS:experiments were performed on left ventricular cardiomyocytes isolated from Wistar rats and SHR (2-2.5 months). Molecular routine tools (RT-PCR, Western blotting, immunocytochemistry) were used for semi-quantitative estimation of α2-AR subtypes. Fluorescence of both the Ca2+-dependent and NO-sensitive probes were used to define functionality of α2-AR, evaluated by changes in the dynamics of spontaneous Ca2+-transients and NO production in cardiomyocytes in response to the α2-AR agonist application. RESULTS:percentage of the three known α2-AR subtypes in Wistar and SHR cardiomyocytes is not principally different. Total amounts of α2A-AR subtype in SHR increases, for both the sarcolemmal and intracellular receptor pools. Total number of α2B-AR is also significantly higher in hypertensive rats with an increase in the sarcolemmal, but not the intracellular immunoreactivity. For α2C-AR subtype, no significant differences between Wistar and SHR were identified, despite the fact that its amounts in cardiomyocytes are somewhat higher than the other two subtypes. Notwithstanding the increased expression of α2-AR subtypes in SHR, α2-AR-agonist guanabenz was ineffective in suppression of spontaneous Ca2+-transients, as well as the lowering of free calcium levels in the cytosol. Guanabenz-induced NO synthesis is well correlated with the Ca2+-loading into sarcoplasmic reticulum and actually decreased in SHR cardiomyocytes. CONCLUSION:data indicate α2-AR dysfunction and ineffectiveness of α2-AR-mediated signaling pathways in this model of cardiovascular pathologies. Results can be used for clinical practice for more effective control of cardiovascular functions in various disease states.

journal_name

Arch Biochem Biophys

journal_title

Archives of biochemistry and biophysics

authors

Kokoz YM,Evdokimovskii EV,Maltsev AV

doi

10.1016/j.abb.2019.108109

subject

Has Abstract

pub_date

2019-10-15 00:00:00

pages

108109

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(19)30450-3

journal_volume

674

pub_type

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Upregulation of α2-adrenoceptor synthesis in SHR cardiomyocytes: Recompense without sense - Increased amounts, impaired commands.