Highlights
- •Prolonged lithium treatment decreases cardiac beta-adrenergic response in rats.
- •Prolonged lithium treatment leads to increased collagen gene expression and atrial tissue fibrosis.
- •Lithium treatment does not affect atrial beta-arrestin gene expression.
Abstract
Lithium is a widely used mood-stabilizing agent; however, it causes a variety of cardiovascular
side effects including sinus node dysfunction. In this study we explored the potential
adverse effects of lithium on cardiac chronotropic responsiveness, atrial tissue histology
and gene expression in rats that were chronically treated with therapeutic doses of
lithium. Male Wistar albino rats were given lithium chloride (2.5 g/kg) orally for
2 or 3 months. Following treatment, the atria were isolated and spontaneously beating
rate and chronotropic responsiveness to β-adrenergic stimulation was evaluated in
an organ bath. Development of cardiac fibrosis was examined by histological methods.
The expression of atrial Col1a1 (collagen I, alpha 1) and β-arrestin2 was also assessed
using quantitative RT-PCR. Treatment with lithium induced a significant hypo-responsiveness
to adrenergic stimulation (P < 0.001) and caused fibrosis in the atrial tissue of treated rats. In addition, the
expression of atrial Col1a1 mRNA was significantly increased in atrial tissues of
lithium-treated animals, while β-arrestin2 mRNA expression did not show a significant
difference compared with control animals. Altogether, these findings indicate that
cardiac chronotropic hypo responsiveness and associated cardiac fibrosis are side
effects of chronic lithium treatment. Moreover, it seems that lithium treatment does
not influence β-arrestin2 mRNA expression.
Keywords
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Article info
Publication history
Published online: September 07, 2018
Accepted:
September 6,
2018
Received in revised form:
August 6,
2018
Received:
March 21,
2018
Identification
Copyright
© 2018 Elsevier B.V. All rights reserved.
