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This Article Full Text Full Text (PDF) All Versions of this Article: 93/1/75    most recent expphysiol.2007.039784v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Freeling, J. Articles by Li, Y.-F. Search for Related Content PubMed PubMed Citation Articles by Freeling, J. Articles by Li, Y.-F.

¹ Division of Basic Biomedical Sciences, Sanford School of Medicine, The University of South Dakota, Vermillion, SD 57069, USA

The inflammatory cytokine tumour necrosis factor (TNF) is known to be a major factor contributing to cardiac remodelling and dysfunction. Parasympathetic nervous system cholinergic function can inhibit TNF expression during systemic infection. In the present study, we tested the effects of a cholinesterase inhibitor, neostigmine, and a muscarinic cholinergic agonist, pilocarpine, on cardiac hypertrophy and TNF levels during pressure overload. Rats with transverse aortic constriction exhibited elevated TNF protein levels in the heart, increased heart weight to body weight ratios (an index of cardiac hypertrophy) and decreased left ventricular diastolic function. Two weeks of infusion with neostigmine (6 µg kg^–1 day^–1) or pilocarpine (0.3 mg kg^–1 day^–1) significantly reduced cardiac hypertrophy, reduced TNF levels and elevated interleukin-10 levels in heart tissues, and improved ventricular function in rats with transverse aortic constriction. Neither of these treatments significantly changed ventricular pressure load. Furthermore, in primary cultured neonatal cardiac cells, treatment with pilocarpine attenuated adrenergic agonist phenylephrine-induced increased TNF expression and [³H]leucine (a marker of protein synthesis) incorporation in the cells. Collectively, both cholinergic agents decreased TNF levels and attenuated cardiac hypertrophy. Since both agents potentially enhanced cholinergic function, the anti-inflammatory action may be involved in the cardioprotective effect of the treatments with these agents.

(Received 31 July 2007; accepted after revision 10 September 2007; first published online 14 September 2007)
Corresponding author Y.-F. Li: Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA. Email: yli01{at}usd.edu