Early events in various forms of experimental acute tubular necrosis in rats.

Metabolic and morphologic changes occurred in the kidneys of rats within 3 hours after inciting acute tubular necrosis by completely clamping the renal blood supply, by intramuscular injections of glycerol, and by subcutaneous injections of HgC12. Although the initial trend was for p-aminohippurate and tetraethylammonium transport to decrease and for oxygen consumption, ammonia production, and gluconeogenesis to increase after glycerol, all of these parameters changed in opposite directions after renal pedicle clamping and after subcutaneous HgC12 (4.7 mg. per kg;). In addition, early morphologic changes in glycerol-injected rats differed from those seen with pedicle clamping and low dose HgC12. With high dose HgC12 (25 mg. per kg.), the metabolic and morphologic changes were somewhere in between those seen with the other insults. Coinciding with early metabolic and morphologic changes, cardiac output and renal blood flow decreased soon after the glycerol was given. On the basis of our findings, we cannot ascribe all of the early metabolic and morphologic changes in the glycerol model to ischemia, and we postulate that the circulating heme proteins may be nephrotoxic to ischemic renal tissue.