AIM: To evaluate the
synergistic action of sodium nitroprusside (SNP) and
isoproterenol (ISO) on canine trachealis, and to
explore the mechanism of synergism. METHODS: Radioimmunoassay was used to assess the amount of cyclic nucleotide in trachealis and phosphodiesterase (PDE) isozyme inhibitors were used as tools. RESULTS: SNP(1￣100 μmol·L -1 ) potentiated ISO (30 μmol·L -1 ) induced relaxation in canine trachealis contracted by methacholine (3 μmol·L -1 ).
Synergistic actions of SNP (100 μmol·L -1 ) and ISO (30 μmol·L -1 ) on canine tracheal relaxation were accompanied by 1 2 and 0 4 fold increments of cAMP content of tracheal smooth muscle compared with SNP and ISO alone, respectively. M&B 22948 (3 μmol·L -1 ), an inhibitor of PDE Ⅴ, increased cAMP accumulation and tracheal relaxation in response to SNP by 4 6 and 1 2 fold, respectively. The PDE Ⅲ inhibitor SK&F 94836 (30 μmol·L -1 ) combined with the PDE Ⅳ inhibitor rolipram (30 μmol·L -1 ) or SNP (100 μmol·L -1 ) combined with SK&F 94836 (30 μmol·L -1 ) increased more ISO induced cAMP accumulation and tracheal relaation than did SK&F 94836, rolipram of SNP. CONCLUSION: The synergistic action of SNP and ISO on canine trachealis is due to inhibition of PDE Ⅲ by SNP induced cGMP accumulation.