Received July 31, 2007
Revised September 6, 2007
Accepted after revision September 10, 2007

¹ University of South Dakota

^* To whom correspondence should be addressed. E-mail: yli01{at}usd.edu.

	Abstract

Inflammatory cytokine TNF is known as a major factor contributing to cardiac remodeling and dysfunction. Parasympathetic nervous system (PSNS) cholinergic function can inhibit TNF expression during systemic infection. In the present study, we tested the effects of a cholinesterase inhibitor, neostigmine (Neo), and a muscarinic cholinergic agonist, pilocarpine (Pilo), on cardiac hypertrophy and TNF levels during pressure overload. Rats with transverse aortic constriction (TAC) 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 Neo (6µg/kg/day) or Pilo (0.3 mg/kg/day), significantly reduced cardiac hypertrophy, reduced TNF levels, and elevated IL-10 levels in heart tissues, and improved ventricular function in rats with TAC. Neither of these treatments significantly changed ventricular pressure load. Furthermore, in primary cultured neonatal cardiac cells, treatment with Pilo attenuated adrenergic agonist phenylephrine (PE)-induced increased TNF expression and 3H-luecine incorporation (a marker of protein synthesis) 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.

Key Words: Autonomic nervous system, Cytokine, Heart