Morphological changes in an early phase of norepinephrine-induced acute renal failure in unilaterally nephrectomized...

The morphological factors contributing to the reduction GFR in an early phase of NE-induced ARF (0.75 microgram/kg/min) were evaluated by comparing renal morphology at the end of NE infusion with that 2 hr later in unilaterally nephrectomized dogs. GFR 2 hr after NE infusion was reduced to 50% of the preinfusion level in a 30 min infusion group (N = 6), to 13% in a 60 min infusion group (N = 7), and to 2% in a 120 min infusin group (N = 5). On the other hand, simultaneous RBF was not significantly reduced in any group. Dilated PT lumina filled with eosinophilic granular materials in paraffin sections fixed in Zenker-Formol or with impacted swollen blebs in Epon sections fixed in diluted Karnovsky's solution and osmium were found diffusely immediately following 60 and 120 min NE infusion, but patchily after 30 min infusion. Similar changes were found 2 hr after the infusion, except that some PTs came to have dilated but transparent lumina in the 60 and 120 min NE infusion groups. Electron microscopic studies revealed that a part of the membrane-bounded cytoplasm of PT cells extruded into the tubular lumen and became impacted swollen blebs during NE-induced ischemia. There was no prominent foot process fusion in any group. It is concluded that the tubular obstruction by impacted swollen blebs generated in PT during ischemia is a major factor responsible for the reduction in GFR in the early phase of NE-induced ARF.