Anti-inflammatory effect of oxytocin in rat myocardial infarction.
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.
Jankowski
Marek
M
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
Bissonauth
Vickram
V
Gao
Lan
L
Gangal
Marius
M
Wang
Donghao
D
Danalache
Bogdan
B
Wang
Yang
Y
Stoyanova
Ekatherina
E
Cloutier
Guy
G
Blaise
Gilbert
G
Gutkowska
Jolanta
J
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
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