Morphology of norepinephrine-induced acute renal failure in the dog

The 40-minute infusion of norepinephrine (NE) into the renal artery of dogs produces a reversible ischemic model of acute renal failure. While the physiology of this model has been extensively studied, no complete description of the pathology exists. This study uses light microscopy and transmission electron microscopy to describe and quantitate the structural and ultrastructural changes which occur in the kidneys of dogs 1, 3, and 24 hours after the intrarenal infusion of 0.75 mg/kg/minute of NE. One hour after a 40-minute NE infusion the majority of convoluted and straight proximal tubules showed apical blebs, loss of brush border, microvillar whorl formation, and mitochondrial condensation and high-amplitude swelling with flocculent densities. Necrotic cells were occasionally seen at 1 hour. The injury was progressive after 3 hours and by 24 hours animals had either complete or partial patchy necrosis of all regions of the proximal tubule. The percentages of injured and necrotic proximal tubules in outer, mid-, and inner cortical regions are presented. We conclude that the extent and pattern of injury seen after NE infusion differs significantly from the renal artery clamping model of ischemia.