title: Ischemia/reperfusion injury is increased and cardioprotection by a postconditioning protocol is lost as cardiac hypertrophy develops in nandrolone treated rats.
abstract: We hypothesized that nandrolone (ND)-abuse induces cardiac hypertrophy, increases myocardial susceptibility to ischemia/reperfusion (I/R) injury, and reduces responsiveness to postconditioning (PostC) cardioprotection. Wistar-rats were ND treated for 2 weeks (short_ND) or 10 weeks (long_ND). Vehicle-treated rats served as controls. Hearts were retrogradely perfused and left ventricular pressure (LVP) was measured before and after 30-min global ischemia. In subgroups of hearts, to induce cardioprotection a PostC protocol (five cycles of 10-s reperfusion and 10-s ischemia) was performed. β-adrenoreceptors, kinases (Akt and GSK-3β) and phosphatases (PP2A sub A and PP2A sub B) were examined by Western blot before and after ischemia. After 120-min reperfusion, infarct size was measured. Short_ND slightly increased cardiac/body weight ratio, but did not affect cardiac baseline nor post-ischemic contractile function or infarct size when compared to vehicle hearts. However, PostC limited cardiac dysfunction much more in short_ND hearts than the other groups. Although cardiac/body weight ratio markedly increased after long_ND, baseline LVP was not affected. Yet, post-ischemic contracture and infarct size were exacerbated and PostC was unable to reduce infarct size and ventricular dysfunction. While short_ND increased phosphatases, non-phosphorylated and phosphorylated Akt, long_ND reduced phosphatase-expression and Akt phosphorylation. Both short_ND and long_ND had no effect on the GSK-3β-phosphorylation but increased the expression of β(2)-adrenoreceptors. In reperfusion, PostC increased Akt phosphorylation regardless of protective effects, but reduced phosphatase-expression in protected hearts only. In conclusion, short_ND improves post-ischemic myocardial performance in postconditioned hearts. However, long_ND increases myocardial susceptibility to I/R injury and abolishes cardioprotection by PostC. This increased susceptibility might be related to steroid-induced hypertrophy and/or to altered enzyme expression/phosphorylation.
authors.affiliation: Department of Clinical and Biological Sciences, "S. Luigi Gonzaga" Hospital, University of Turin, Orbassano, TO, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Penna
authors.forename: F
authors.initials: F
authors.lastname: Tullio
authors.forename: M-G
authors.initials: MG
authors.lastname: Perrelli
authors.forename: F
authors.initials: F
authors.lastname: Moro
authors.forename: G
authors.initials: G
authors.lastname: Abbadessa
authors.forename: F
authors.initials: F
authors.lastname: Piccione
authors.forename: V
authors.initials: V
authors.lastname: Carriero
authors.forename: S
authors.initials: S
authors.lastname: Racca
authors.forename: P
authors.initials: P
authors.lastname: Pagliaro
mesh_terms: D045930:Anabolic Agents / Q000633:toxicity*; D000818:Animals; D015153:Blotting, Western; D006332:Cardiomegaly / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D019157:Ischemic Preconditioning, Myocardial; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D009277:Nandrolone / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D045930:Anabolic Agents; D009277:Nandrolone