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 (30 micrograms/min) inhibited hypoxia-induced vasoconstriction (IC50 = 6.3 X 10(-5) M) and vasoconstriction due to bolus injection of angiotensin II (IC50 = 8.2 X 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 2 microgram leukotriene C4. Thus, db-cAMP inhibited pulmonary vascular reactivity nonspecifically.
Sakai
A
A
Cardiovascular Pulmonary Research Laboratory, University of Colorado, Denver 80262.
Voelkel
N F
NF
D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D013004:Somatostatin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D000628:Aminophylline; D013004:Somatostatin; D003994:Bucladesine