Nitric oxide causes hyporeactivity to phenylephrine m isolated perfused livers from endotoxin-treated rats

C. M. Pastor, T. R. Billiar*

*Corresponding author for this work

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41 Scopus citations


Systemic vascular hyporeactivity to vasoconstrictors has been described in rats following endotoxin administration. Inducible nitric oxide synthase (iNOS) expression is known to occur in the liver in endotoxemia, but consequences of iNOS induction on hepatic hemodynamics are unknown. The reactivity of the hepatic circulation to phenylephrine was tested in perfused livers from normal rats and rats previously injected with endotoxin (20 mg/kg ip). In control rats (n = 5), phenylephrine-induced portal pressure increases were similar in livers perfused with Krebs-Henseleit-bicarbonate (KHB) buffer, KHB plus the NOS inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 1 mM), or KHB plus the substrate for NO synthesis, L-arginine (1 mM). In contrast, livers from endotoxin-treated rats (n = 5) exhibited a marked reduction in the vasoconstrictive response to phenylephrine (14.6 vs. 55.1% in livers from control rats, p < 0.05). Perfusion with L-NMMA restored the phenylephrine response, and the L-NMMA effect was reversible with L-arginine. Perfusate NO2/-/NO3/- and guanosine 3',5'-cyclic monophosphate (cGMP) levels were increased in endotoxin-treated rats and significantly reduced by L-NMMA perfusion. In control livers, the NO donor S-nitroso-N-acetyl-DL- penicillamine blocked the portal pressure increase after phenylephrine administration. These results suggest that rat hepatic circulation takes part in the systemic vascular hyporeactivity to vasoconstrictors observed in endotoxemia and that NO is involved in this hyporeactivity to phenylephrine.

Original languageEnglish
Pages (from-to)G177-G182
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number1 31-1
StatePublished - 1995
Externally publishedYes


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