POSSIBLE INVOLVEMENT OF ENDOTHELIN PEPTIDES AND L-ARGININE NITRIC-OXIDE PATHWAY ON THE EFFECT OF ENDOTOXIN IN THE RABBIT ISOLATED-PERFUSED KIDNEY

ESCHERICHIA COLI endotoxin (LPS) when infused through the renal artery of the rabbit isolated perfused kidney prepared as constant pressure mode, caused a decrease in flow rate and kidney weight indicating its primary vasoconstrictor effect. This effect was predominant in kidneys from rabbits pretreated with LPS. Endothelin-1 at a concentration of 10(-10) M and big endothelin-1 at a concentration of 10(-8) M produced equal vasoconstrictor effects in kidney. Addition of endothelin conve rting enzyme inhibitor, phosphoramidon, to the perfusion medium at a c oncentration of 10(-6) M caused a reduction in the effects of both LPS and big ET-1 without altering the vasoconstrictor effect of ET-1. How ever, addition of methylene blue (10(-5) M), a soluble guanylate cycla se inhibitor and N(G)-nitro-L-arginine-methyl ester (10(-6) M) to the perfusion medium caused a potentiation in the vasoconstrictor effect o f LPS. Indomethacin at a concentration of 10(-6) M did not alter the e ffect of LPS. These results were taken as evidence for the participati on of endothelin peptides and the L-arginine-nitric oxide pathway in t he effect of LPS in rabbit isolated perfused kidney.