b2-adrenoreceptor overexpression is beneficial against ischemia/reperfusion (I/R) injury. Whether b-adrenoreceptors are involved in postconditioning (PostC) is unknown. We investigated whether nandrolone-decanoate (ND)-pretreatment can modulate (1) b-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 b2-adrenoreceptors. Isolated rat hearts from NDpretreated (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 b2- 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 b2-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 NDpretreated 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 inhearts of ND-pretreated than untreated-animals. ICI-118.551 abolished NDprotection and PostC-protection both in ND-pretreated and untreated hearts. Data show that two-weeks ND-pretreatment induces 1) an overexpression of b2-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 b2-adrenoreceptor activation.

Synergistic effects against post-ischemic cardiac dysfunction by sub-chronic nandrolone pretreatment and postconditioning: role of b2-adrenoreceptors

PENNA, Claudia;ABBADESSA, Giuliana;MANCARDI, Daniele;TULLIO, FRANCESCA;PICCIONE, Francesca;RACCA, Silvia Anna;PAGLIARO, Pasquale
2008

Abstract

b2-adrenoreceptor overexpression is beneficial against ischemia/reperfusion (I/R) injury. Whether b-adrenoreceptors are involved in postconditioning (PostC) is unknown. We investigated whether nandrolone-decanoate (ND)-pretreatment can modulate (1) b-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 b2-adrenoreceptors. Isolated rat hearts from NDpretreated (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 b2- 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 b2-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 NDpretreated 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 inhearts of ND-pretreated than untreated-animals. ICI-118.551 abolished NDprotection and PostC-protection both in ND-pretreated and untreated hearts. Data show that two-weeks ND-pretreatment induces 1) an overexpression of b2-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 b2-adrenoreceptor activation.
59
645
659
beta-receptors; cardioprotection; ischemia/reperfusion; nandrolone; postconditioning.
C. PENNA; G. ABBADESSA; D. MANCARDI; F. TULLIO; F. PICCIONE; A. SPACCAMIGLIO; S. RACCA; P. PAGLIARO.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/56598
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