Both KT-362 and TMB-8 produce vasodilation via mechanisms that are thought to involve inhibition of intracellular calcium mobilization. This study compares the vasodilation produced by these two agents with their effects on phosphatidylinositol hydrolysis in canine femoral artery. KT-362 and TMB-8 both produced concentration-related relaxation of femoral artery rings precontracted with 10 μM norepinephrine. Both vasodilators also produced relaxation in rings precontracted with 3 μM serotonin (5-hydroxytryptamine) at concentrations of 30 μM and greater. KT-362 significantly inhibited norepinephrine-induced phosphatidylinositol hydrolysis at concentrations of 1 μM and greater and inhibited serotonin-induced phosphatidylinositol hydrolysis at concentrations of 10 μM and greater. TMB-8 had no effect on norepinephrine stimulation of phosphatidylinositol hydrolysis at concentrations up to 100 μM. Therefore, these studies demonstrate that while KT-362 and TMB-8 have very similar vasodilator effects on precontracted femoral arteries, only KT-362 produces vasodilation as a result of inhibition of phosphatidylinositol hydrolysis.
|Number of pages||4|
|Journal||Journal of Vascular Medicine and Biology|
|State||Published - Jan 1 1991|