Dibutyryl cyclic adenosine monophosphate inhibits pulmonary vasoconstriction

The effects of the cell-permeable dibutyryl derivative of cyclic AMP on the vascular reactivity of isolated perfused rat lungs were examined. In lungs perfused with homologous blood, pulmonary arterial infusion of db-cAMP (30µg/min) inhibited hypoxia-induced vasoconstriction (IC₅₀=6.3×10^?5 M) and vasoconstriction due to bolus injection of angiotensin II (IC₅₀=8.2×10^?5 M). Cyclic AMP phosphodiesterase inhibition by aminophylline acted synergistically with db-cAMP in the reduction of hypoxia-induced vasoconstriction. Somatostatin, an inhibitor of adenylate cyclase, prevented the decay of hypoxic vasoconstriction typically observed in isolated lungs, suggesting that a rise in intracellular cAMP may occur during hypoxic vasoconstriction as a consequence of activation of the adenylate cyclase. In lungs perfused with cell and protein-free salt solution, db-cAMP inhibited both initial and prolonged vasoconstriction following bolus injection of 2µg leukotriene C₄. Thus, db-cAMP inhibited pulmonary vascular reactivity nonspecifically.