Dibutyryl cAMP inhibits endotoxin-induced increases in pulmonary vascular resistance and fluid filtration coefficient in the perfused rat lung.
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.
Takeoka
M
M
Research Center on Aging and Adaptation, Shinshu University School of Medicine, Matsumoto, Japan. mictake@gipac.shinshu-u.ac.jp
Sakai
A
A
Ueda
G
G
Ge
R L
RL
Ishizaki
T
T
Panos
R J
RJ
Taniguchi
S
S
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D006152:Cyclic GMP / Q000494:pharmacology; D004731:Endotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D066298:In Vitro Techniques; D008297:Male; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012477:Salmonella enteritidis; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*
D004731:Endotoxins; D003994:Bucladesine; D006152:Cyclic GMP