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Neostigmine and pilocarpine attenuated tumour necrosis factor α expression and cardiac hypertrophy in the heart with pressure overload
Author(s) -
Freeling Jessica,
Wattier Kristina,
LaCroix Carly,
Li YiFan
Publication year - 2008
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2007.039784
Subject(s) - medicine , endocrinology , pressure overload , pilocarpine , cardiac function curve , phenylephrine , cholinergic , muscle hypertrophy , bethanechol , tumor necrosis factor alpha , muscarinic acetylcholine receptor , blood pressure , heart failure , receptor , cardiac hypertrophy , psychiatry , epilepsy
The inflammatory cytokine tumour necrosis factor α (TNFα) is known to be a major factor contributing to cardiac remodelling and dysfunction. Parasympathetic nervous system cholinergic function can inhibit TNFα 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 TNFα levels during pressure overload. Rats with transverse aortic constriction exhibited elevated TNFα 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 TNFα 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 TNFα expression and [ 3 H]leucine (a marker of protein synthesis) incorporation in the cells. Collectively, both cholinergic agents decreased TNFα 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.