N G ‐NITRO‐ l ‐ARGININE METHYL ESTER POTENTIATES ANAPHYLACTIC VENOCONSTRICTION IN RAT PERFUSED LIVERS

SUMMARY1 The effects of the nitric oxide (NO) synthase inhibitor N G ‐nitro‐ l ‐arginine methyl ester ( l ‐NAME) on anaphylaxis‐induced venoconstriction were examined in rat isolated livers perfused with blood‐free solutions in order to clarify the role of NO in anaphylactic venoconstriction. 2 Rats were sensitized with ovalbumin (1 mg) and, 2 weeks later, livers were excised and perfused portally in a recirculating manner at a constant flow with Krebs’–Henseleit solution. The antigen (ovalbumin; 0.1 mg) was injected into the reservoir 10 min after pretreatment with l‐NAME (100 mmol/L) or d ‐NAME (100 mmol/L) and changes in portal vein pressure (Ppv), hepatic vein pressure (Phv) and perfusate flow were monitored. In addition, concentrations of the stable metabolites of NO ( and ) were determined in the perfusate using an HPLC–Griess system. 3 The antigen caused hepatic venoconstriction, as evidenced by an increase in Ppv from a mean (SEM) baseline value of 7.7 ± 0.1 cmH 2 O to a peak of 21.4 ± 1.1 cmH 2 O at 3 min in d ‐NAME‐pretreated livers. Pretreatment with l‐NAME augmented anaphylactic venoconstriction, as reflected by a higher Ppv (27.4 ± 0.8 cmH 2 O) after antigen than observed following d ‐NAME pretreatment. The addition of l ‐arginine, a precursor for the synthesis of NO, reversed the augmentation of anaphylactic venoconstricion by l ‐NAME. This suggests that hepatic anaphylaxis increased the production of NO, which consequently attenuated anaphylactic venoconstriction. However, perfusate NO x levels did not increase significantly after antigen in livers pretreated with either l ‐NAME or d ‐NAME. 4 In conclusion, l ‐NAME potentiates rat anaphylactic hepatic venoconstriction, suggesting that NO contributes to the attenuation of the venoconstriction. However, this functional evidence was not accompanied by corresponding changes in perfusate NO x concentrations.