title: Anti-inflammatory effect of oxytocin in rat myocardial infarction.
abstract: While an increasing amount of evidence demonstrates the homeostatic functions of the cardiac oxytocin (OT) system, less is known about the role of this hormone in the injured heart. The current study examined the effect of OT infusion on cell apoptosis, expression of proliferating cell nuclear antigen (PCNA) and inflammation in the acute and subacute phases of myocardial infarction (MI). Prior MI male Sprague-Dawley rats were infused subcutaneously with OT 25 or 125 ng/(kg h) for 3 or 7 days. Saline-treated MI and sham-operated rats served as controls. Echocardiography and analysis of cardiac sections were used to disclose OT actions. Left ventricular fractional shortening, estimated to be 46.0 +/- 1.8% in sham controls, declined to 21.1 +/- 3.3% in vehicle-treated MI rats and was improved to 34.2 +/- 2.1 and to 30.9 +/- 2.5% after treatment with OT 25 and 125 ng/(kg h), respectively. OT infusion resulted in: (1) increase of cells expressing PCNA in the infarct zone, diminished cell apoptosis and fibrotic deposits in the remote myocardium; (2) suppression of inflammation by reduction of neutrophils, macrophages and T lymphocytes; (3) depression of the expression of proinflammatory cytokines tumor necrosis factor-alpha and interleukin-6 with promotion of transforming growth factor-beta. OT treatment reduced expression of atrial and brain natriuretic peptides in the infarcted ventricle, as well as the concentration of both peptides in the circulation. These results indicate that continuous OT delivery reduces inflammation and apoptosis in infarcted and remote myocardium, thus improving function in the injured heart.
authors.affiliation: Centre de Recherche, Centre Hospitalier de l'Université de Montréal (CRCHUM), Hôtel-Dieu, Pavillon Jeanne-Mance 3840, rue Saint-Urbain, Montreal, QC H2W 1T8, Canada. marek.jankowski@umontreal.ca
authors.forename: Marek
authors.initials: M
authors.lastname: Jankowski
authors.forename: Vickram
authors.initials: V
authors.lastname: Bissonauth
authors.forename: Lan
authors.initials: L
authors.lastname: Gao
authors.forename: Marius
authors.initials: M
authors.lastname: Gangal
authors.forename: Donghao
authors.initials: D
authors.lastname: Wang
authors.forename: Bogdan
authors.initials: B
authors.lastname: Danalache
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Ekatherina
authors.initials: E
authors.lastname: Stoyanova
authors.forename: Guy
authors.initials: G
authors.lastname: Cloutier
authors.forename: Gilbert
authors.initials: G
authors.lastname: Blaise
authors.forename: Jolanta
authors.initials: J
authors.lastname: Gutkowska
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004452:Echocardiography; D006334:Heart Function Tests; D007962:Leukocytes / Q000473:pathology; D008297:Male; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D009205:Myocarditis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D045265:Natriuretic Peptides / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010120:Oxytocics / Q000494:pharmacology / Q000627:therapeutic use*; D010121:Oxytocin / Q000494:pharmacology / Q000627:therapeutic use*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020107:Troponin T / Q000378:metabolism
chemical_list: D016207:Cytokines; D045265:Natriuretic Peptides; D010120:Oxytocics; D018809:Proliferating Cell Nuclear Antigen; D020107:Troponin T; D010121:Oxytocin; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat