7-NITROINDAZOLE, BUT NOT L-NAME OR AMINOGUANIDINE, ATTENUATES ANAPHYLACTIC HYPOTENSION IN CONSCIOUS RATS

Abstract

The roles of NO and isozymes of NO synthase (NOS) are not known in anaphylactic hypotension of unanesthetized rats. Effects of inhibition of NOS, iNOS, and nNOS by N-nitro-L-arginine methyl ester (L-NAME), aminoguanidine, and 7-nitroindazole, respectively, were determined on the antigen-induced systemic hypotension and portal hypertension in conscious Sprague-Dawley rats sensitized with the ovalbumin antigen. The MAP and portal venous pressure were directly and simultaneously measured. The control rats showed a decrease in MAP along with an increase in portal venous pressure but did not die within 48 h after antigen injection. In the rats pretreated with the nonselective NOS inhibitor L-NAME (10 mg/kg), MAP before and after antigen administration was significantly higher than that of the control rats, but the net decrease in MAP and increase in portal venous pressure were rather greater than those of the control, resulting in fatal outcome within 12 h after antigen administration. In contrast, pretreatment with the relatively selective nNOS inhibitor 7-nitroindazole (50 mg/kg) substantially attenuated anaphylactic hypotension over 20 min after antigen administration, whereas the relatively selective iNOS inhibitor aminoguanidine (100 mg/kg) did not affect it. In conclusion, in anaphylactic hypotension of unanesthetized rats, NO derived from nNOS, but not from iNOS, may be involved, and the nonselective NOS inhibitor L-NAME is lethal.