title: Adenine sulfate improves cardiac function and the cardiac cholinergic system after myocardial infarction in rats.
abstract: Recent studies have shown that vagal activation may have an important therapeutic implication for myocardial infarction (MI), but effective strategies remain unexplored. Here, we investigate whether adenine sulfate can preserve cardiac function and the cholinergic system against MI. Rats were treated with adenine sulfate for three weeks after coronary ligation. Cardiac function was assessed by hemodynamics. The muscarinic M(2) receptor and cholinesterase-positive nerves were semi-quantified by immunochemical and histochemical staining. The maximal binding capacity (B(max)) of muscarinic receptors, determined by radioligand binding assay, showed that cardiac function was impaired in MI rats. Adenine sulfate reversed MI-induced reduction of mean artery pressure and left ventricular systolic pressure and elevation of left ventricular end-diastolic pressure. Moreover, adenine sulfate also increased nitric oxide (NO) and nitric oxide synthase (NOS) activity. The amelioration was accompanied by a reversal of the infarction-induced reduction of cholinesterase-positive nerves and M(2)-receptor expression and B(max) in the adenine sulfate high dose group. Meanwhile, adenine sulfate treatment corrected the disorder of cardiac redox state by reduction in maleic dialdehyde and increase in superoxide dismutase. In conclusion, adenine sulfate exerts cardioprotection against MI and ameliorates NO production. Changes in cardiac vagal distribution density and M(2)-receptor expression raise the possibility that improvement of the cardiac cholinergic system is involved in adenine sulfate-induced cardioprotective effects.
authors.affiliation: Department of Pharmacology, School of Life Science and Technology, Xi'an Jiaotong University, Xi’an, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Xiao-Jiang
authors.initials: XJ
authors.lastname: Yu
authors.forename: Dong-Ling
authors.initials: DL
authors.lastname: Li
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Xu
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Ke-Yu
authors.initials: KY
authors.lastname: Ren
authors.forename: Jian-Kang
authors.initials: JK
authors.lastname: Liu
authors.forename: Wei-Jin
authors.initials: WJ
authors.lastname: Zang
mesh_terms: D000225:Adenine / Q000494:pharmacology*; D000447:Aldehydes / Q000032:analysis; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010919:Placebos; D011869:Radioligand Assay; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000447:Aldehydes; D002317:Cardiovascular Agents; D010919:Placebos; D011950:Receptors, Cholinergic; C015977:malealdehyde; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D000225:Adenine