Anisodamine at higher concentrations in inhibiting alpha-adrenergic responses in isolated canine blood vessels

The present study was designed to examine the effect of higher concentration of anisodamine on alpha-adrenergic responses in isolated canine blood vessels. Up to 10(-3) mol/L, anisodamine did not significantly affect the responses of saphenous vein to alpha 2-adrenergic agonist UK-14, 304. In contrast, anisodamine (10(-5), 10(-4), 10(-3) mol/L) caused the concentration-response curves of femoral artery to norepinephrine (pA2 = 4.81 +/- 0.11) to phenylephrine (pA2 = 4.86 +/- 0.20) shift markedly. However, the antagonism on the alpha 1-adrenergic responses of canine femoral artery to norepinephrine and phenylephrine by higher concentrations of anisodamine produces dose ratios which yield a linear Schild regression with a slope less than unity, indicating an inequilibrium between agonist, antagonist, and receptors. The probable mechanisms involved are discussed.