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The role of nitric oxide in the vascular hyporesponsiveness to methoxamine in portal hypertensive rats

Authors

  • Fa-Yauh Lee,

    1. Hepatic Hemodynamic Laboratory, Veterans Affairs Medical Center, West Haven, Connecticut 06516
    2. Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510
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  • Agustin Albillos,

    1. Hepatic Hemodynamic Laboratory, Veterans Affairs Medical Center, West Haven, Connecticut 06516
    2. Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510
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  • Luis A. Colombato,

    1. Hepatic Hemodynamic Laboratory, Veterans Affairs Medical Center, West Haven, Connecticut 06516
    2. Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510
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  • Roberto J. Groszmann M.D.

    Corresponding author
    1. Hepatic Hemodynamic Laboratory, Veterans Affairs Medical Center, West Haven, Connecticut 06516
    2. Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510
    • Hepatic Hemodynamic Laboratory/111J, Veterans Affairs Medical Center, 950 Campbell Ave., West Haven, CT 06516
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Abstract

This study examined whether an increased activity of the endothelium-derived relaxing factor, nitric oxide, may account for the hyporesponsiveness to vasoconstrictors in portal hypertension. We performed dose-response curves to methoxamine, an α-adrenoceptor agonist, with and without Nω-nitro-L-arginine, a specific inhibitor of nitric oxide synthesis, in experimental portal hypertension. Partial portal vein—ligated or sham-operated rats were pretreated with a continuous intravenous infusion of either Nω-nitro-L-arginine (50 μg · kg−1 · min−1) or saline. Thirty minutes after starting the infusion of Nω-nitro-L-arginine or saline an infusion of methoxamine (10, 30 and 100 μg · kg−1 · min−1) was added. Total peripheral resistance was calculated from mean arterial pressure and cardiac index. Repeated measurements of cardiac index were performed by a thermodilution technique. In portal vein—ligated rats pretreated with saline, the increase in total peripheral resistance after methoxamine infusion was significantly less than that of sham-operated rats (0.2 ± 0.1 vs. 1.0 ± 0.3, 0.6 ± 0.1 vs. 1.6 ± 0.3 and 3.7 ± 0.5 vs. 6.1 ± 0.7 mm Hg · ml−1 · min · 100 gm, p < 0.05, methoxamine 10, 30 and 100 μg · kg−1 · min−1, respectively). In the presence of Nω-nitro-L-arginine, the change in total peripheral resistance after methoxamine infusion was similar in both groups (p > 0.05). In conclusion, this study demonstrates that a vascular hyporesponsiveness to methoxamine is present in portal vein—ligated rats and that this hyporesponsiveness is reversed by blockade of nitric oxide. This suggests that nitric oxide plays an important role in the arterial vasodilation observed in portal hypertensive states. (HEPATOLOGY 1992;16:1043–1048.)

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