Endotoxin-induced renal failure - I. A role for altered renal microcirculation

The pathogenesis of sepsis-induced renal failure is multi-factorial and onl y partially understood. In these studies we evaluated intrarenal microcircu latory changes during endotoxemia and the potential role of nitric oxide (N O) and endothelin in these changes. In anesthetized rats endotoxin infusion [lipopolysaccharide (LPS), Escherichia coli serotype 0127:B8; 10 mg/kg/h] resulted in hypotension and a transient enhancement of renal blood flow, wi th cortical vasodilation and a loss of outer medullary vasodilatory respons e to hypotension. The initial cortical vasodilation was abolished by the NO synthase inhibitor NG-nitro-L-arginine methyl ester, but not by indomethac in. Direct NO measurements disclosed a gradual rise in cortical NO, despite the waning vasodilatory effect, suggesting antagonizing vasoconstrictive s timuli. In rats pretreated by LPS (1 mg/kg i.p. 1 day earlier) the renal bl ood flow was reduced to 55% of that of controls. Moreover, the vasodilatory response to LPS infusion was converted into profound cortical and medullar y vasoconstriction. In these preconditioned rats the endothelin receptor an tagonist bosentan evoked a vasodilatory response and attenuated the vasocon strictive reaction to LPS infusion. The infusion of another LPS (E. coli se rotype 0111:B4) exerted predominant and protracted renal vasodilation witho ut hypotension. In conclusion, different LPS exert diverse systemic and ren al hemodynamic responses. The 0127:B8 serotype attenuates renal medullary v asodilation during hypotension, exerts transient cortical vasodilation, and following repeated exposure induces profound renal vasoconstriction. NO an d endothelin participate in LPS-induced vascular responses that may predisp ose to hypoxic tubular damage. Copyright (C) 2000 S. Karger AG, Basel.