Disturbance of I1-imidazoline receptor signal transduction in cardiomyocytes of Spontaneously Hypertensive Rats

Abstract

Imidazoline receptor of the first type (I₁R) in addition to the established inhibition of sympathetic neurons may mediate the direct control of myocellular functions. Earlier, we revealed that I₁-mediated signaling in the normotensive rat cardiomyocytes suppresses the nitric oxide production by endothelial NO synthase, impairs sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA) activity, and elevates intracellular calcium in the cytosol. Also, I₁-agonists counteract β-adrenoceptor stimulation effects in respect to voltage-gated calcium currents. This study ascertains the I₁R signal transduction in the normotensive Wistar and SHR cardiomyocytes. Reduction of Ca²⁺-currents by rilmenidine, a specific agonist of I₁R, ensued from the phosphatidylcholine-specific phospholipase C-mediated activation of protein kinase C. There is a stimulation of serine/threonine phosphatase activity. In SHR cardiomyocytes, both the rilmenidine, and putative endogenous ligand, agmatine, almost twofold less effectively reduced L-type of Ca²⁺-currents. Average mRNA level of Nischarin, established functional component of I₁R, is slightly decreased in SHR, as well as the intracellular Nischarin pool immunolabeled in the cytosol of SHR cardiomyocytes. Disturbance of I₁R signal transduction in SHR may aggravate the development of this cardiovascular pathology.

Keywords: Adrenergic stress; Agmatine; L-type Ca(2+)-channel; PKC; Rilmenidine.