N(G)-nitro-L-arginine methyl ester potentiates anaphylactic venoconstriction in rat perfused livers.

Abstract

1. 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 micromol/L) or D-NAME (100 micromol/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 cmH2O to a peak of 21.4 +/- 1.1 cmH2O 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 cmH2O) 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 NOx 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 NOx concentrations.

• Authors: Toshishige Shibamoto, Takaharu Ishibashi, Tomohiro Shimo, Sen Cui, Hiromichi Takano, Hideaki Tsuchida, Matomo Nishio, Yasutaka Kurata
• Journal: Clinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 33 Issue 11 Pg. 1073-7 (Nov 2006) ISSN: 0305-1870 [Print] Australia
• PMID: 17042917 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nitric Oxide
• Ovalbumin
• Arginine
• NG-Nitroarginine Methyl Ester

Topics

• Anaphylaxis (chemically induced)
• Animals
• Arginine (pharmacology)
• Liver (metabolism)
• Male
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide (metabolism)
• Ovalbumin (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Vasoconstriction (drug effects)