DIBUTYRYL-CAMP IMPROVES SYSTEMIC VASOCONSTRICTION CAUSED BY ENDOTOXININ DOGS

We studied whether dibutyryl cyclic adenosine monophosphate (DbcAMP), which freely penetrates into the cells, improves systemic vasoconstric tion caused by endotoxin in dogs. Thirteen anesthetized dogs were rand omized into three groups. The endotoxin (ETX) group (n = 5) received o nly Escherichia coli endotoxin (3 mg . kg(-1), intravenously). The ETX + DbcAMP group (n = 5) received DbcAMP (6 mg . kg(-1), intravenously) 30 min before the administration of endotoxin. The DbcAMP group recei ved the same dose of DbcAMP 30 min after administration of saline. In the ETX group, systemic blood pressure and cardiac index significantly decreased, and systemic Vascular resistance significantly increased, while in the me + DbcAMP group, increases in systemic and pulmonary va scular resistances after the administration of endotoxin were attenuat ed. DbcAMP did not cause hemodynamic changes in normal dogs. Plasma co ncentrations in thromboxane B-2 in the ETX group were higher than in t he ETX + DbcAMP group. Also, the change in plasma cyclic AMP concentra tions showed a good logarithmic correlation with the change in plasma thromboxane B-2 concentrations after the administration of endotoxin ( r =.908, Log (Delta TxB(2)) = -.002(Delta cAMP) + 3.786). We conclude that DbcAMP improves systemic vasoconstriction caused by endotoxin in dogs. The beneficial mechanism of DbcAMP on systemic vasoconstriction after the administration of endotoxin may be partially due to inhibit ion of thromboxane B-2.