Kinin antagonist does not protect against the hypotensive response to endotoxin, anaphylaxis or acute pancreatitis

The vasodilator bradykinin (Bk) has long been though to participate in shock induced by endotoxemia, anaphylaxis and acute pancreatitis. Recently developed kinin antagonists have made it possible to test this hypothesis. We studied the effect of two of them. DArg0Hyp3-Thi5.8-DPhe7-Bk (45 and 220 micrograms/kg/min) and Lys-Lys-Hyp2-Thi5.8-DPhe7-Bk (100 micrograms/kg/min) on the early hypotensive response to Escherichia coli lipopolysaccharide (LPS). Rats infused with the antagonist vehicle were used as controls. At 45 micrograms/kg/min, DArg0-Hyp3-Thi5.8-dPhe7-Bk prevented the hypotensive response to high doses of Bk; however, neither antagonist prevented the hypotensive response to LPS. Circulating kinins measured 3 min after injecting LPS or vehicle were similar (16.3 +/- 1.4 vs. 26.0 +/- 7.2 pg/ml; P greater than .23). In allergically sensitized rats, 500 micrograms/kg/min DArg0-Hyp3-Thi5.8-DPhe-7-Bk did not alter the hypotensive (anaphylactic) response to antigen challenge (P greater than .38). Similarly, hypotension caused by development of acute pancreatitis in rats was not prevented by infusion of DArg0-Hyp3-Thi5.8-DPhe7-Bk at 200 micrograms/kg/min, 10 min) (P greater than .69). These results indicate that in the rate formation of kinins is not a major contributor to the hypotensive response observed in early endotoxemia, anaphylaxis and acute pancreatitis.