title: Neostigmine and pilocarpine attenuated tumour necrosis factor alpha expression and cardiac hypertrophy in the heart with pressure overload.
abstract: The inflammatory cytokine tumour necrosis factor alpha (TNF alpha) is known to be a major factor contributing to cardiac remodelling and dysfunction. Parasympathetic nervous system cholinergic function can inhibit TNF alpha 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 alpha levels during pressure overload. Rats with transverse aortic constriction exhibited elevated TNF alpha 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 microg kg(-1) day(-1)) or pilocarpine (0.3 mg kg(-1) day(-1)) significantly reduced cardiac hypertrophy, reduced TNF alpha 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 alpha expression and [3H]leucine (a marker of protein synthesis) incorporation in the cells. Collectively, both cholinergic agents decreased TNF alpha 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.
authors.affiliation: Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Freeling
authors.forename: Kristina
authors.initials: K
authors.lastname: Wattier
authors.forename: Carly
authors.initials: C
authors.lastname: LaCroix
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Li
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000502:physiology; D006332:Cardiomegaly / Q000517:prevention & control*; D002478:Cells, Cultured; D003251:Constriction, Pathologic / Q000503:physiopathology; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D016753:Interleukin-10 / Q000096:biosynthesis; D008297:Male; D009388:Neostigmine / Q000494:pharmacology*; D009929:Organ Size / Q000502:physiology; D010277:Parasympathomimetics / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology*; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013566:Sympathomimetics / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D016276:Ventricular Function
chemical_list: D010277:Parasympathomimetics; D013566:Sympathomimetics; D014409:Tumor Necrosis Factor-alpha; D010862:Pilocarpine; D016753:Interleukin-10; D010656:Phenylephrine; D009388:Neostigmine