N(G)-nitro-L-arginine methyl ester, but not methylene blue, attenuates anaphylactic hypotension in anesthetized mice

To clarify the role of NO in mouse anaphylactic hypotension, effects of a nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), on antigen-induced hypotension and portal hypertension were determined in anesthetized BALB/c mice. Systemic arterial pressure (Psa), central venous pressure (Pcv), and portal venous pressure (Ppv) were directly and simultaneously measured. Mice were first sensitized with ovalbumin, and then the injection of antigen was used to decrease Psa and increase Ppv. Pretreatment with L-NAME (1 mg/kg) attenuated this antigen-induced systemic hypotension, but not the increase in Ppv. The effect of inhibitors of soluble guanylate cyclase on anaphylactic hypotension were studied with either methylene blue (3.0 mg/kg) or 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (10 mg/kg). Neither modulated any antigen-induced changes. Furthermore, methylene blue did not improve systemic hypotension induced by Compound 48/80 (4.5 mg/kg), a mast cell degranulator, which can produce non-immunological anaphylactoid reactions. These data show in anesthetized BALB/c mice that L-NAME attenuated anaphylactic hypotension without affecting portal hypertension. This beneficial effect of L-NAME appears not to depend on the soluble guanylate cyclase pathway.