Effects of ischemia and reperfusion injury on calcium sensitivity of mitochondrial permeability transition pore (mPTP) in hypertrophied hearts

PÉREZ NUÑEZ I; FANTINELLI JC; MOSCA SM

Ciudad Autónoma de Buenos Aires

Congreso; XVII Reunión de la Sección latinoamericana de la Internacional Society for Heart Research; 2009

Federación Argentina de Cardiología- Sección latinoamericana de la ISHR

Calcium overload occurring during ischemia and reperfusion (I-R), is implicated in the mPTP opening, event associated to myocardial reversible and irreversible injury. The aim of the present study was to compare PTP calcium sensitivity in mitochondria isolated from hearts of spontaneously hypertensive rats (SHR) and normotensive rats (Wistar, W), recently extracted from the animal (C), perfused during 3 hs (P) or submitted to 35 min of global ischemia and 2 hs of reperfusion. The mitochondria were isolated by differential centrifugation and the mPTP opening was measured through calcium-mediated light scattering (LS) at 520 nm using a spectrofluorometer. In mitochondria of group C a dosis-response curve was performed using 20, 50, 100, 200, 500 and 1000mmol/L of calcium. In W rats, 200 mmol/L of calcium produces the maximum LS (1.20 ± 0.20 a.u.) and in SHR the value was significantly lower (0.50 ± 0.09 a.u.). When that dose of calcium was administered to mito of groups P and I-R, the LS for SHR was 0.13 ± 0.05 and 0.18 ± 0.02 a.u. (NS), and for W was 0.24 ± 0.06 and 0.10 ± 0.02 a.u. (p <0.05), respectively. Our data reveal that mPTP of SHR hearts without any intervention possesses a lower sensitivity to calcium than those of W rats and that the I-R did not modify it. These results are suggesting that in ¨in situ¨ conditions the majority of mPTP of hearts from SHR is opened.