Role of nitric oxide in the functional response to ischemia-reperfusion of heart mitochondria from hyperthyroid rats.
We investigated the role of nitric oxide (NO) in the mitochondrial derangement associated with the functional response to ischemia-reperfusion of hyperthyroid rat hearts. Mitochondria were isolated at 3000 g from hearts subjected to ischemia-reperfusion, with or without N(omega)-nitro-L-arginine (L-NNA, an NO synthase inhibitor). During reperfusion, hyperthyroid hearts displayed tachycardia and low functional recovery. Their mitochondria exhibited O(2) consumption similar to euthyroid controls, while H(2)O(2) production, hydroperoxide, protein-bound carbonyl and nitrotyrosine levels, and susceptibility to swelling were higher. L-NNA blocked the reperfusion tachycardic response and increased inotropic recovery in hyperthyroid hearts. L-NNA decreased mitochondrial H(2)O(2) production and oxidative damage, and increased respiration and tolerance to swelling. Such effects were higher in hyperthyroid preparations. These results confirm the role of mitochondria in ischemia-reperfusion damage, and strongly suggest that NO overproduction is involved in the high mitochondrial dysfunction and the low recovery of hyperthyroid hearts from ischemia-reperfusion. L-NNA also decreased protein content and cytochrome oxidase activity of a mitochondrial fraction isolated at 8000 g. This and previous results suggest that the above fraction contains, together with light mitochondria, damaged mitochondria coming from the heaviest fraction, which has the highest cytochrome oxidase activity and capacity to produce H(2)O(2). Therefore, we propose that the high mitochondrial susceptibility to swelling, favoring mitochondrial population purification from H(2)O(2)-overproducing mitochondria, limits hyperthyroid heart oxidative stress.
Venditti
P
P
Dipartimento di Fisiologia Generale ed Ambientale, Università di Napoli, V. Mezzocannone 8, 80134, Napoli, Italy.
De Rosa
R
R
Cigliano
L
L
Agnisola
C
C
Di Meo
S
S
D000818:Animals; D006861:Hydrogen Peroxide / Q000378:metabolism; D006980:Hyperthyroidism / Q000503:physiopathology*; D008297:Male; D008929:Mitochondria, Heart / Q000502:physiology*; D008933:Mitochondrial Swelling; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D010101:Oxygen Consumption; D051381:Rats; D017208:Rats, Wistar
D019335:Nitroarginine; D009569:Nitric Oxide; D006861:Hydrogen Peroxide