A possible role of the tubuloglomerular feedback mechanism in ischemic or hypoxic injury studied in the isolated rabbit kidney perfused with autologous blood

Abstract

Since functional and morphological damage after ischemic or hypoxic injury in the isolated perfused rabbit kidney is unknown, the present study starts to examine kidney function and morphology after ischemia and hypoxia. Subsequently, the study focuses on the question whether TGF is involved in the deterioration of the kidney function after exposure to hypoxia. Therefore it was aimed to inhibit TGF at three different levels: 1. Inhibition of the sensor of the TGF. This might be achieved with furosemide via inhibition of the transport at the macula densa cells, the initial step of the TGF. 2. A rightward resetting of the TGF via induction of a modulator, nitric oxide, of the TGF mechanism. This is aimed via addition of L-arginine. 3. Inhibition of adenosine, the suggested mediator of the TGF mechanism. This is pursued via a selective inhibition of the A1 and the A2 adenosine receptor. According to the introduction, adenosine and NO might also be involved in the protection against ischemia, elicited by IPC. Therefore the possible protective effects of IPC and AP against ischemia are examined in the isolated perfused kidney. It would be relevant for the understanding of the pathophysiological mechanism if the question could be answered whether IPC alters the sensitivity of the TGF. Model As discussed previously, systemic influences may affect the pathophysiology of acute renal failure. In order to study the intrinsic functional changes of the kidney itself, the isolated kidney preparation is used to exclude systemic effects. Since perfusion in the presence of erythrocyte prevents injury to the mTAL and reduces the FE Na+ , the isolated rabbit kidney perfused with autologous blood is used as a model to study the pathophysiology of acute renal failure in the present study. This model was functionally characterized in control conditions and it was shown that this preparation did not deteriorate before two hours of blood perfusion.