DIBUTYRYL cAMP IMPROVES SYSTEMIC VASOCONSTRICTION CAUSED BY ENDOTOXIN IN DOGS

Abstract

We studied whether dibutyryl cyclic adenosine monophosphate (DbcAMP), which freely penetrates into the cells, improves systemic vasoconstriction caused by endotoxin in dogs. Thirteen anesthetized dogs were randomized into three groups. The endotoxin (ETX) group (n = 5) received only 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 received 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 ETX + DbcAMP group, increases in systemic and pulmonary vascular resistances after the administration of endotoxin were attenuated. DbcAMP did not cause hemodynamic changes in normal dogs. Plasma concentrations in thromboxane B2 in the ETX group were higher than in the ETX + DbcAMP group. Also, the change in plasma cyclic AMP concentrations showed a good logarithmic correlation with the change in plasma thromboxane B2 concentrations after the administration of endotoxin (r = .908, log (delta T x B2) = -.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 inhibition of thromboxane B2.