Tohoku J. Exp. Med., 1997, 183 (4)

Dibutyryl CAMP Inhibits Endotoxin-Induced Increases in Pulmonary Vascular Resistance and Fluid Filtration Coefficient in the Perfused Rat Lung

MICHIKO TAKEOKA, AKIO SAKAI, GOU UEDA, RI-LI GE, TAKESHI ISHIZAKI,1 RALPH J. PANOS2 and SHUN-ICHIRO TANIGUCHI

Research Center on Aging and Adaptation, Shinshu University School of Medicine, Matsumoto 390, 1The Third Department of Internal Medicine, Fukui Medical School, Fukui 910-11, and 2Pulmonary Division, Northwestern University Medical School, Chicago, IL 60611, USA

  • We investigated the effects of pre-treatment with dibutyryl cAMP (db-cAMP) or cGMP on endotoxin-induced hemodynamic changes and pulmonary vascular permeability in isolated perfused rat lungs. Intraperitoneal injection of Salmonella enteritidis endotoxin (2 mg/kg) caused increases in pulmonary arterial resistance (Ra) after venous reservoir elevation, in pulmonary filtration coefficient (Kf) and in lung wet-to-dry (W/D) weight ratio. Pre-treatment with db-cAMP blocked endotoxin-induced increases in Ra, Kf and W/D weight ratio. Pre-treatment with cGMP attenuated only the increase in Ra caused by endotoxin. Moreover, administration of db-cAMP 2 hours after endotoxin injection attenuated the increase in Ra induced by endotoxin treatment. The increases in Kf and W/D weight ratio caused by endotoxin were not affected by post-treatment with db-cAMP. Since the increases in Ra, Kf and W/D weight ratio caused by endotoxin were blocked by pre-treatment with db-cAMP, agents that increase intracellular cAMP level may be useful to prevent acute pulmonary vascular injury. ations or not.
    Key words--- filtration coefficient; venous reservoir elevation; pulmonary vascular resistance; pulmonary microvascular pressure; isolated perfused rat lung
    © 1997 Tohoku University Medical Press

    Tohoku J. Exp. Med., 1997, 183, 273-284
    Address for reprints: Michiko Takeoka, Ph. D., Research Center on Aging and Adaptation, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390, Japan.
    e-mail: mictake@gipac.shinshu-u.ac.jp

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