title: Synergistic effects against post-ischemic cardiac dysfunction by sub-chronic nandrolone pretreatment and postconditioning: role of beta2-adrenoceptor.
abstract: Beta(2)-adrenoreceptor overexpression is beneficial against ischemia/reperfusion (I/R) injury. Whether beta-adrenoreceptors are involved in postconditioning (PostC) is unknown. We investigated whether nandrolone-decanoate (ND)-pretreatment can modulate (1) beta-adrenoreceptor expression and (2) post-ischemic cardiac function in response to I/R and PostC. Finally, we tested whether cardioprotection can be prevented by the inhibition of beta(2)-adrenoreceptors. Isolated rat hearts from ND pretreated (15 mg/kg/day i.m., for 14 days) and untreated-animals underwent 30-min ischemia and 120-min reperfusion. In subgroups, at the end of ischemia a PostC protocol (five cycles of 10-s reperfusion and 10-s ischemia) was applied and/or a beta(2)-adrenoreceptor blocker, ICI-118.551 (10 microM), was infused. Left ventricular pressure (LVP) was measured with an electromanometer, and infarct-size was evaluated using nitro-blue-tetrazolium staining. ND-pretreatment increased beta(2)-adrenoreceptor expression, but did not alter cardiac-weight, LVP and maximum rate of increase of LVP (dP/dt(max)). After I/R, infarct-size was smaller in ND-pretreatment than in untreated-animals. Infarct-size was also reduced by PostC, both in untreated and ND-pretreated animals. Contracture was less marked in ND-pretreated animals. PostC reduced contracture in both ND-pretreated and untreated hearts. Moreover, PostC improved post-ischemic recovery of developed LVP and dP/dt(max) much more in earts of ND-pretreated than untreated-animals. ICI-118.551 abolished ND protection and PostC-protection both in ND-pretreated and untreated hearts. Data show that two-weeks ND-pretreatment induces 1) an overexpression of beta(2)-ARs without cardiac hypertrophy and 2) improves the post-ischemic diastolic and systolic cardiac function. Intriguingly, ND-pretreatment potentiates the improvement of systolic function induced by postconditioning via beta(2)-adrenoreceptor activation.
authors.affiliation: Dipartimento di Scienze Cliniche e Biologiche, Universita di Torino, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Penna
authors.forename: G
authors.initials: G
authors.lastname: Abbadessa
authors.forename: D
authors.initials: D
authors.lastname: Mancardi
authors.forename: F
authors.initials: F
authors.lastname: Tullio
authors.forename: F
authors.initials: F
authors.lastname: Piccione
authors.forename: A
authors.initials: A
authors.lastname: Spaccamiglio
authors.forename: S
authors.initials: S
authors.lastname: Racca
authors.forename: P
authors.initials: P
authors.lastname: Pagliaro
mesh_terms: D045930:Anabolic Agents / Q000494:pharmacology*; D000818:Animals; D006332:Cardiomegaly / Q000517:prevention & control; D002316:Cardiotonic Agents / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D008365:Manometry; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077603:Nandrolone Decanoate; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects* / Q000235:genetics
chemical_list: D045930:Anabolic Agents; D002316:Cardiotonic Agents; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; C026777:ICI 118551; D009277:Nandrolone; D000077603:Nandrolone Decanoate