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Hemodynamic effects of combined treatment with somatostatin analogue (SMS 201-995) and low-dose isosorbide dinitrate on portal hypertension in conscious cirrhotic rats

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Abstract

The authors investigated whether combined treatment with the somatostatin analogue, SMS 201-995, and low-dose isosorbide dinitrate enhanced the hemodynamic effects of the individual agents on rats with thioacetamide-induced cirrhosis. Four groups of cirrhotic rats received SMS 201-995 (0.1 μg·min−1·kg−1), isosorbide dinitrate (10 μ·min−1·kg−1), both agents, or placebo, respectively. Hemodynamics were measured serially in conscious rats, using a radioactive microsphere method. SMS 201-995 reduced portal venous inflow 21±4% and portal pressure 17±3%. Isosorbide dinitrate decreased portal venous inflow 20±4%, by inducing splanchnic vasoconstriction mediated by low pressure baroreflexes, and this agent also decreased portal pressure, by 14±2%. Portal venous resistance rose 7.6±3% with isosorbide dinitrate alone, but decreased 18±4% with combination therapy. This effect may have been induced by the pronounced vasodilatory effect of isosorbide dinitrate on the venous vasculature, since the reflex splanchnic vasoconstriction that occurs with low-dose isosorbide dinitrate disappears when this agent is combined with SMS 201-995. The decrease in portal pressure was more marked (22±4%) and changes in systemic hemodynamics were milder with the combined treatment. It was concluded that combination therapy with SMS 201-995 and low-dose isosorbide dinitrate may be beneficial for portal hypertension in liver cirrhosis.

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Authors and Affiliations

  1. Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji Kamigyo-ku, 602, Kyoto, Japan

    Naoki Hori, Takeshi Okanoue, Yoshihiko Sawa, Yoshito Itoh, Takashi Mori, Shiro Takami & Kei Kashima

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  1. Naoki Hori
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  2. Takeshi Okanoue
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  3. Yoshihiko Sawa
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  4. Yoshito Itoh
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  5. Takashi Mori
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  6. Shiro Takami
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  7. Kei Kashima
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Hori, N., Okanoue, T., Sawa, Y. et al. Hemodynamic effects of combined treatment with somatostatin analogue (SMS 201-995) and low-dose isosorbide dinitrate on portal hypertension in conscious cirrhotic rats. J Gastroenterol 29, 460–468 (1994). https://doi.org/10.1007/BF02361244

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  • DOI: https://doi.org/10.1007/BF02361244

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