Cardioprotective effect of ischemic preconditioning is preserved in food-restricted senescent rats.
Ischemic preconditioning (PC) has been proposed as an endogenous form of protection against-ischemia reperfusion injury. We have shown that PC does not prevent postischemic dysfunction in the aging heart. This phenomenon could be due to the reduction of cardiac norepinephrine release, and it has also been previously demonstrated that age-related decrease of norepinephrine release from cardiac adrenergic nerves may be restored by caloric restriction. We investigated the effects on mechanical parameters of PC against 20 min of global ischemia followed by 40 min of reperfusion in isolated hearts from adult (6 mo) and "ad libitum"-fed and food-restricted senescent (24 mo) rats. Norepinephrine release in coronary effluent was determined by high-performance liquid chromatography. Final recovery of percent developed pressure was significantly improved after PC in adult hearts versus unconditioned controls (85.2 +/- 19% vs. 51.5 +/- 10%, P < 0.01). The effect of PC on developed pressure recovery was absent in ad libitum-fed rats, but it was restored in food-restricted senescent hearts (66.6 +/- 13% vs. 38.3 +/- 11%, P < 0.05). Accordingly, norepinephrine release significantly increased after PC in both adult and in food-restricted senescent hearts, and depletion of myocardial norepinephrine stores by reserpine abolished the PC effect in both adult and in food-restricted senescent hearts. We conclude that PC reduces postischemic dysfunction in the hearts from adult and food-restricted but not in ad libitum-fed senescent rats. Despite the possibility of multiple age-related mechanisms, the protection afforded by PC was correlated with increased norepinephrine release, and it was blocked by reserpine in both adult and food-restricted senescent hearts. Thus caloric restriction may restore PC in the aging heart probably via increased norepinephrine release.
Abete
Pasquale
P
Cattedra di Geriatria, Dipartmento di Medicina Clinica, Scienze Cardiovasculari ed Immunologiche, Università degli Studi di Napoli FedericoII, Naples, Italy. p.abete@cds.unina.it
Testa
Gianluca
G
Ferrara
Nicola
N
De Santis
Domenico
D
Capaccio
Pina
P
Viati
Luisa
L
Calabrese
Claudio
C
Cacciatore
Francesco
F
Longobardi
Giancarlo
G
Condorelli
Mario
M
Napoli
Claudio
C
Rengo
Franco
F
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000375:Aging; D000818:Animals; D001783:Blood Flow Velocity; D001835:Body Weight; D003326:Coronary Circulation; D002149:Energy Intake; D005508:Food Deprivation; D006352:Heart Ventricles / Q000033:anatomy & histology; D006439:Hemodynamics; D019194:Ischemic Preconditioning; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology; D009929:Organ Size; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D012110:Reserpine / Q000494:pharmacology; D014693:Ventricular Fibrillation / Q000209:etiology / Q000517:prevention & control
D018759:Adrenergic Uptake Inhibitors; D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D012110:Reserpine; D009638:Norepinephrine; D011224:Prazosin