ENDOTOXIN-INDUCED ACUTE-RENAL-FAILURE IN THE RAT - EFFECTS OF URODILATIN AND DILTIAZEM ON RENAL-FUNCTION

Acute renal failure (ARF) due to endotoxins is a common problem in cli nical medicine. Endotoxins are released from the outer membrane of the gram-negative bacterial envelope and are composed of lipopolysacchari des (LPS). Although systemic hypotension often is present, LPS-induced ARF is characterized by marked intrarenal vasoconstriction. Both calc ium channel blockers and natriuretic peptides are able to antagonize v asoconstricting signals and have been reported to exert beneficial eff ects in toxic and ischemic ARF: We investigated the effects of diltiaz em (Dil, 300 mu g/kg) or urodilatin (Uro, 40 mu g/kg) or a combination of both (same doses) on renal function in early LPS-induced ARF: One hour after induction of ARF by i.v. injection of LPS glomerular filtra tion rate (GFR, clearance of fluorescence-marked inulin) was distinctl y reduced to about 54% of basal values. In the following infusion peri od (60 min) a significant increase of GFR was observed with diltiazem (1.54 +/- 0.11 ml/min), urodilatin (1.60 +/- 0.10 ml/min) and the comb ination of both drugs (1.66 +/- 0.04 ml/min) compared to controls (1.1 7 +/- 0.08 ml/min). Combined administration did not cause additive eff ects. Also 60 and 120 minutes after stopping of drug infusion elevated GFR could be maintained in all experimental groups. Due to their vaso relaxing activity both Uro and Dil induced a decrease of mean arterial blood pressure in comparison with controls and revealed remarkable di uretic and natriuretic activity. In conclusion our results underline t hat marked intrarenal vasoconstriction in LPS-induced ARF can be antag onized by the well known relaxing potency of Uro and Dil towards vascu lar smooth muscle and mesangial cells. Both Uro and Dil were capable o f improving suppressed renal function in the early phase of LPS-induce d ARF in the rat as long as severe systemic hypotension is absent.