- •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.
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.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Autonomic Neuroscience: Basic and Clinical
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Acute cardiomyopathy precipitated by lithium: is there a direct toxic effect on cardiac myocytes?.Am. J. Emerg. Med. 2015; 331330.e1-5
- Bipolar disorder.N. Engl. J. Med. 2004; 351: 476-486
- Lithium and the heart. Unanswered questions.Chest. 1988; 93: 166-169
- Therapeutic potential of mood stabilizers lithium and valproic acid: beyond bipolar disorder.Pharmacol. Rev. 2013; 65: 105-142
- Fibrosis: a structural modulator of sinoatrial node physiology and dysfunction.Front. Physiol. 2015; 6: 37
- Dual regulation of G proteins and the G-protein-activated K+ channels by lithium.Proc. Natl. Acad. Sci. U. S. A. 2014; 111: 5018-5023
- Lithium: clinical considerations in internal medicine.Am. J. Med. 2006; 119: 478-481
- Cirrhosis is associated with development of tolerance to cardiac chronotropic effect of endotoxin in rats.Liver Int. 2013; 33: 368-374
- Overview of the mechanism of action of lithium in the brain: fifty-year update.J. Clin. Psychiatry. 2000; 61: 5-15
- Lithium: still a major option in the management of bipolar disorder.CNS Neurosci. Ther. 2012; 18: 219-226
- Role of circulating fibrocytes in cardiac fibrosis.Chin. Med. J. 2016; 129: 326-331
- Lithium: a review of its metabolic adverse effects.J. Psychopharmacol. 2006; 20: 347-355
- Renal fibrosis mRNA classifier: validation in experimental Lithium-induced interstitial fibrosis in the rat kidney.PLoS One. 2016; 11e0168240
- Sinus node dysfunction associated with lithium therapy in a child.Tex. Heart Inst. J. 2002; 29: 200-222
- Glycogen synthase kinase-3 is essential for beta-arrestin-2 complex formation and lithium-sensitive behaviors in mice.J. Clin. Invest. 2011; 121: 3756-3762
- Lithium-induced sinus node disease at therapeutic concentrations: linking lithium-induced blockade of sodium channels to impaired pacemaker activity.Can. J. Cardiol. 2007; 23: 229-232
- Lithium and kidney: (a study of renal biopsy in Lithium patients).Indian J. Psychiatry. 1981; 23: 52-57
- Chronic interstitial fibrosis in the rat kidney induced by long-term (6-mo) exposure to lithium.Am. J. Physiol. Ren. Physiol. 2013; 304: F300-F307
- Symptomatic sinus node abnormalities following lithium carbonate therapy.Am. J. Med. 1975; 59: 285-287
Published online: September 07, 2018
Accepted: September 6, 2018
Received in revised form: August 6, 2018
Received: March 21, 2018
© 2018 Elsevier B.V. All rights reserved.