Role of mitochondria in ischemic acute renal failure.
Ischemic ARF is characterized by progressive mitochondrial accumulation of Ca++ which is inversely correlated with the level of oxidative phosphorylation. At least two possibilities exist which would be compatible with these data 1) depressed respiration leads to Ca++ accumulation or 2) increased mitochondrial Ca++ leads to reduced mitochondrial respiration. We favor the latter hypothesis for the reasons outlined above; furthermore, this conclusion is supported by the observations of Lehninger, made some 20 years ago: first, that either oxidative phosphorylation or mitochondrial Ca++ accumulation can be accomplished by intact mitochondria but that these events cannot occur simultaneously and second, that Ca++ accumulation takes precedence over oxidative phosphorylation. Our observation made during post-ischemic reflow that mitochondrial Ca++ accumulation occurs to a significant degree, strongly suggest a potential role for mitochondrial Ca++ overload in the pathogenesis of ARF. Nevertheless, this is not an irreversible pathogenetic process. Clearly, impermeant solutes, vasodilators and Ca++ membrane blockers will alter the natural history of this injury and prevent the severity of the functional defect. A common mechanism of action may involve direct or indirect modification of cellular Ca++ overload in renal vascular and epithelial tissue. The vascular smooth muscle may then revert to a less constricted state with a subsequent more rapid recovery of renal blood flow and that the renal epithelial cell death may be minimized thereby reducing tubular obstruction.
D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004285:Dogs; D004721:Endoplasmic Reticulum / Q000378:metabolism; D066298:In Vitro Techniques; D007511:Ischemia / Q000150:complications / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D010101:Oxygen Consumption; D051381:Rats
D008274:Magnesium; D002118:Calcium