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Type V phosphodiesterase inhibition modulates endogenous immunoreactivities of endothelin-1 and endothelial nitric oxide synthase in pulmonary arteries in rats with monocrotaline-induced pulmonary hypertension

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Research in Experimental Medicine

Abstract

We evaluated the effects of oral administration of E4021 (100 mg/ kg/day), a type V phosphodiesterase inhibitor, on immunoreactivities of endothelin-1, endothelin receptors, and nitric oxide synthases in pulmonary arteries in a rat model of pulmonary hypertension. Immunoreactivities of endothelin-1 and endothelial nitric oxide synthase were observed significantly less frequently, together with significant reduction of right ventricular overload and medial thickening in rats treated with E4021 than in the control with mono-crotaline on day 28. The levels of plasma endothelin-1 and serum nitrite and nitrate were significantly lower in rats that received E4021 than in the control with monocrotaline. Oral administration of E4021 modulates endogenous immunoreactivities of endothelin-1 and endothelial nitric oxide synthase with the improvement or right ventricular overload and medial thickening.

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Authors and Affiliations

  1. Department of Infectious Diseases and Applied Immunology, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedi, Minato-ku, Tokyo, 108, Japan

    Takashi Takahashi & Aikichi Iwamoto

  2. Department of Laboratory Medicine, Gunma University School of Medicine, Gunma, Japan

    Tsugiyasu Kanda & Isao Kobayashi

  3. Second Department of Internal Medicine, Gunma University School of Medicine, Gunma, Japan

    Hiroyuki Sumino, Masahiro Inoue, Kunio Sato, Tetsuo Sakamaki & Ryozo Nagai

Authors
  1. Takashi Takahashi
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  2. Tsugiyasu Kanda
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  3. Hiroyuki Sumino
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  4. Masahiro Inoue
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  5. Kunio Sato
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  6. Tetsuo Sakamaki
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  7. Isao Kobayashi
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  8. Aikichi Iwamoto
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  9. Ryozo Nagai
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Correspondence to Takashi Takahashi.

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Takahashi, T., Kanda, T., Sumino, H. et al. Type V phosphodiesterase inhibition modulates endogenous immunoreactivities of endothelin-1 and endothelial nitric oxide synthase in pulmonary arteries in rats with monocrotaline-induced pulmonary hypertension. Res. Exp. Med. 197, 319–328 (1997). https://doi.org/10.1007/s004330050080

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  • DOI: https://doi.org/10.1007/s004330050080

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