Is alpha-adrenoceptor blockade responsible for atropine flush?

Toxic amounts of atropine usually, and therapeutic doses occasionally, dilate cutaneous blood vessels, especially those in the blush area (atropine flush). However, the mechanism of this anomalous vascular response is unknown. We, therefore, investigated this action of atropine not only in functional but also in binding studies with isolated rat aorta and brain, respectively. Endothelium-denuded rat thoracic aortic rings were contracted with norepinephrine, U46619 (9,11-dideoxy-11alpha,9alpha-epoxymethanoprostaglandin F2alpha, thromboxane A2 receptor agonist) and KCl, and the relaxation in response to atropine was recorded. The norepinephrine-, but not the U46619- or KCL-mediated contraction was relaxed by atropine. Atropine caused a rightward parallel shift of the phenylephrine concentration-contraction curve with a pA2 value of 6.57 (slope 0.58), but did not affect the concentration-contraction curve for U46619. In rat cerebral cortex homogenates, atropine displaced [3H]prazosin with Ki values of 3.33 nM and 0.19 microM, respectively. These results suggest that even though atropine has low affinity for the alpha-adrenoceptor, it possesses characteristics similar to those of a competitive ligand for the alpha-adrenoceptor. Thus, atropine, especially at high concentrations, has direct alpha-adrenoceptor blocking activity, which may account, at least in part, for atropine flush.