F0F1ATP synthase activity is differently modulated by coronary reactive hyperemia before and after ischemic preconditioning in the goat

Claudia Penna, Pasquale Pagliaro, Raffaella Rastaldo, Francesca Di Pancrazio, Giovanna Lippe, Donatella Gattullo, Daniele Mancardi, Michele Samaja, Gianni Losano, Irene Mavelli
2004 American Journal of Physiology. Heart and Circulatory Physiology  
Mavelli. F0F1 ATP synthase activity is differently modulated by coronary reactive hyperemia before and after ischemic preconditioning in the goat. .-The amplitude of coronary reactive hyperemia (CRH), elicited by 15 s of ischemia, is reduced in hearts subjected to 5 min of ischemic preconditioning (IP). F 0F1 ATP synthase activity and ATP concentration are also altered by IP. We hypothesized that F 0F1 ATP synthase is differently modulated by the inhibitor protein IF 1 during CRH elicited
more » ... (CRH np) and after (CRHprec) IP. Hemodynamic parameters were recorded in 10 anesthetized goats. Myocardial biopsies were obtained before IP (C np), during CRHnp, 4 and 6 min after the onset of CRH np, after IP (Cprec), during CRHprec, and 4 min after CRH prec. F0F1 ATP synthase activity, ATP concentration, and ATPto-ADP ratio (ATP/ADP) were determined. Compared with CRH np, IP blunted CRH prec. F0F1 ATP synthase activity transiently increased during CRH np, decreased 4 min after CRHnp, and returned to control 2 min later; it was lower after IP (C prec) and did not change during and after CRH prec. All these changes in activity were modulated by IF1. During CRH np, ATP concentration and ATP/ADP were reduced compared with C np and began to rise 6 min thereafter. During Cprec, both parameters were transiently reduced but increased during and after CRH prec. Hence, during CRHnp, F0F1 ATP synthase activity transiently increases and then decreases significantly. The shortlasting inhibition of the enzyme may explain why a few seconds of occlusion do not induce IP. After IP, F 0F1 ATP synthase activity is blunted, and it is not affected by a subsequent 15 s of occlusion, which induces a blunted CRH prec. These results suggest that postischemic long-lasting inhibition of F 0F1 ATP synthase activity may be a feature of the preconditioned heart. The increase in ATP concentration after preconditioning is in agreement with previous reports of reduced ATP hydrolysis by cytoplasmic ATPases. coronary circulation; energy metabolism; ischemia; mitochondria THE IMMEDIATE SOURCE OF ENERGY for myocardial contraction is provided by the hydrolysis of ATP. Although ATP hydrolysis is carried out by a number of ATPases, its resynthesis is mainly mediated by mitochondrial F 0 F 1 ATP synthase, which couples the transport of protons across the mitochondrial inner membrane to the synthesis of ATP (6, 7, 12). However, when the proton electrochemical gradient across the inner membrane Address for reprint requests and other correspondence: P. Pagliaro, Dipartimento di
doi:10.1152/ajpheart.00327.2004 pmid:15217795 fatcat:de5svaxpk5eg3cbto6mdpi76hu