The effects of endothelin receptor blockade in the course of experimental postishaemic acute renal failure

Abstract

The main goal of this study was to examine the efficacy of endothelin (ET) receptor blockade in the course of experimental postischaemic acute renal failure (ARF). Experiments were performed on male adult Wistar rats. The right kidney was removed before renal ischaemia (by clamping the left renal artery for 45 minutes). The experimental groups received either bosentan (ETA/ETB-receptor antagonist; 10mg/kg/b.m) or vehicle (saline) in the femoral vein 20 minutes before, during and 20 minutes after ischaemia. All parameters were measured 24 hours after reperfusion. The obtained results clearly demonstrate that bosentan yields beneficial effect on ARF. Bosentan improves both renal haemodynamic and functional parameters after ARF, while lesions of tubular epithelial cells, the principal targets of injury in ARF are less serious in bosentan-treated rats than in the control ARF rats. This strongly suggests that endothelins have an important role in the development of ischaemia/'reperfusion injury and contributes to the promotion of bosentan in future clinical practice.

Uticaji blokade receptora endotelinskih peptida na tok postishemične eksperimentalne akutne bubrežne insuficijencije (ABI), predstavljali su glavni cilj naših istraživanja. Eksperimenti su izvođeni na odraslim pacovima Wistar soja. Urađena je netrektomija desnog bubrega, a leva bubrežna arterija je klemovana u trajanju od 45 minuta. Eksperimentalne grupe su prekofemoralne vene primale Hi bpsentan (antagonist ETA/ETB-receptora) Hi fiziološki rastvor, kontinuirano, 20 minuta pre, tokom i 20 minuta posle perioda ishemije. Svi parametri su mereni 24 časa nakon perioda ishemije. Dobijeni rezultati jasno pokazuju da bozentan iskazuje povoljne uticaje na tok ABI. Bozentan poboljšava bubrežne hemodinamske i funkcionalne parametre, a lezije epitelnih ćelija tubula (glavnih mesta oštećenja u ABI), su manje izražene kod pacova tretiranih bosentanom, negp kod kontrolnih životinja sa ABI. Sve to navodi na zaključak da endotelini imaju uticaja u razvoju ishemično/reperfuzionih oštećenja u ABI i da bosentan poseduje potencijal za primenu u kliničkoj praksi.