Pharmacological modification of pulmonary vascular injury: possible role of cAMP.
Experiments were designed to test the hypothesis that drugs which increase adenosine 3',5'-cyclic monophosphate (cAMP) in the lung would prevent the pulmonary hypertension and the increase in vascular permeability caused by the infusion of the oxidant lipid peroxide, tert-butyl hydroperoxide (t-bu-OOH), in isolated rabbit lungs perfused with Krebs-Henseleit buffer. Pretreatment with indomethacin or verapamil was also studied, since these drugs block the increase in pulmonary arterial pressure caused by t-bu-OOH. Indomethacin or verapamil prevented the pulmonary hypertension but did not prevent the increase in permeability caused by t-bu-OOH. Consequently, indomethacin or verapamil treatment partially reduced the gain in lung weight caused by t-bu-OOH. In contrast, pretreatment with isoproterenol, prostaglandin E1, or a cAMP analogue not only prevented the pulmonary hypertension but also inhibited the increase in vascular permeability caused by t-bu-OOH. Consequently, these drugs completely blocked the gain in lung weight caused by t-bu-OOH. Posttreatment with aminophylline or the cAMP analogue also significantly reduced the gain in lung weight caused by t-bu-OOH. These results indicate that pharmacological therapy can reduce the pulmonary hypertension and the increase in vascular permeability caused by the infusion of a lipid hydroperoxide. Since isoproterenol, aminophylline, prostaglandin E1, and a cAMP analogue all had similar effects, the results suggest that the likely common mechanism for their protective effect is an increase in cAMP.
D000527:Alprostadil / Q000627:therapeutic use; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D000242:Cyclic AMP / Q000502:physiology*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D007213:Indomethacin / Q000627:therapeutic use; D007545:Isoproterenol / Q000627:therapeutic use; D008297:Male; D010545:Peroxides / Q000494:pharmacology; D011817:Rabbits; D014700:Verapamil / Q000627:therapeutic use; D020122:tert-Butylhydroperoxide
D010545:Peroxides; D020122:tert-Butylhydroperoxide; D014700:Verapamil; D000242:Cyclic AMP; D000527:Alprostadil; D007545:Isoproterenol; D007213:Indomethacin