Synergistic effects against post-ischemic cardiac dysfunction by sub-chronic nandrolone pretreatment and postconditioning: role of beta2-adrenoreceptors

• Autorzy: Penna C. , Abbadessa G. , Mancardi D. , Tullio F. , Piccione F. , Spaccamiglio A. , Racca S. , Pagliaro P.
• Języki publikacji: EN

Abstrakty

EN

ß2-adrenoreceptor overexpression is beneficial against ischemia/reperfusion (I/R) injury. Whether ß-adrenoreceptors are involved in postconditioning (PostC) is unknown. We investigated whether nandrolone-decanoate (ND)-pretreatment can modulate (1) ß-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 ß2-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 ß2-adrenoreceptor blocker, ICI-118.551 (10 µM), was infused. Left ventricular pressure (LVP) was measured with an electromanometer, and infarct-size was evaluated using nitro-blue-tetrazolium staining. ND-pretreatment increased ß2-adrenoreceptor expression, but did not alter cardiac-weight, LVP and maximum rate of increase of LVP (dP/dtmax). 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/dtmax much more in hearts 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 ß2-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 ß2-adrenoreceptor activation.

Słowa kluczowe

EN

cardioprotection; nandrolone; post-ischaemic cardiac dysfunction; beta-receptor; ischaemia-reperfusion; beta2-adrenoreceptor; heart; synergistic effect

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2008
• Tom: 59
• Numer: 4
• Opis fizyczny: p.645-659,fig.,ref.

Twórcy

autor

Penna C.

• Universita di Torino, Ospedale S.Luigi, Regione Gonzole, 10043 Orbassano [TO] Italy

autor

Abbadessa G.

autor

Mancardi D.

autor

Tullio F.

autor

Piccione F.

autor

Spaccamiglio A.

autor

Racca S.

autor

Pagliaro P.