Endothelin in a model of acute ischemic renal dysfunction: Modulating action of atrial natriuretic factor

This study was undertaken to investigate circulating endothelin (ET) and associated renal hemodynamics in the acute ischemic renal dysfunction associated with suprarenal aortic cross-clamping (ACC) in the presence and absence of prostaglandin inhibition in the anesthetized dog. Second, the modulating action of exogenous atrial natriuretic factor (ANF) was also investigated. In Group I (ACC; N = 6), ACC was performed in the absence of prostaglandin inhibition. No change in mean arterial pressure, GFR, RBF, renal vascular resistance, or ET was noted 2 h after reperfusion when compared with baseline values. In the presence of prostaglandin inhibition with indomethacin (10 mg/kg iv) (Group II, ACC + INDO; N = 10), an increase in plasma ET was first noted to be elevated above baseline ET in Group I as well as during and 2 h after ACC in association with a reduction in GFR, marked renal vasoconstriction, and a sustained increase in arterial pressure. To evaluate the role of the kidney in this increase in ET, another group (Group III, ACC + INDO + NEPH; N = 6) was investigated in the presence of prostaglandin inhibition, and bilateral renal artery clamping was performed 30 min before ACC and maintained through-out the protocol to simulate nephrectomy. In this group, plasma ET concentrations did not increase during ACC. Because ANF may antagonize the renal actions of ET in vivo and may suppress ET release in vitro, the action of ANF upon GFR and plasma ET was evaluated in Group IV (ACC + INDO + ANF; N = 6). In this group, in the presence of prostaglandin inhibition, plasma ET increased during ACC and returned to baseline after ACC in response to ANF, with a return of GFR, RBF, and renal vascular resistance to baseline. Mean arterial pressure decreased as well to baseline levels. This study demonstrates that ACC results in acute renal dysfunction associated with an increase in circulating ET only in the presence of prostaglandin inhibition, suggesting an important role of prostaglandins in the regulation of circulating ET. This study also suggests that the kidney is involved in the elevation of ET seen in this model. Last, ANF attenuates this increase in ET and maintains GFR and RBF.