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 endotheHn converting enzyme inhibitor, phosphoramidon, to the perfusion medium at a concentration of 10(−6) M caused a reduction in the effects of both LPS and big ET-1 without altering the vasoconstrictor effect of ETol. However, addition of methylene blue (10(−5) M), a soluble guanylate cyclase inhibitor and N(G)-nitro-L-arginine-methyl ester (10(−6) M) to the perfusion medium caused a potentiation in the vasoconstrictor effect of LPS. Indomethacin at a concentration of 10(−6) M did not alter the effect of LPS. These results were taken as evidence for the participation of endothelin peptides and the L-arginine-nitric oxide pathway in the effect ofLPS in rabbit isolated perfused kidney.