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 (a tropine flush). However, the mechanism of this anomalous vascular resp onse is unknown. We, therefore, investigated this action of atropine n ot only in functional but also in binding studies with isolated rat ao rta and brain, respectively. Endothelium-denuded rat thoracic aortic r ings were contracted with norepinephrine, U46619 (9,11-dideoxy-11 alph a,9 alpha-epoxymethanoprostaglandin F-2 alpha, thromboxane A(2) recept or agonist) and KCl, and the relaxation in response to atropine was re corded. The norepinephrine-, but not the U46619- or KCl-mediated contr action was relaxed by atropine. Atropine caused a rightward parallel s hift of the phenylephrine concentration-contraction curve with a pA(2) value of 6.57 (slope 0.58), but did not affect the concentration-cont raction curve for U46619. In rat cerebral cortex homogenates, atropine displaced [H-3]prazosin binding with a K-i value of 1.21 mu M, while phentolamine and clonidine displaced [H-3]prazosin with K-i values of 3.33 nM and 0.19 mu M, respectively. These results suggest that even t hough atropine has low affinity for the alpha-adrenoceptor, it possess es characteristics similar to those of a competitive ligand for the al pha-adrenoceptor. Thus, atropine, especially at high concentrations, h as direct alpha-adrenoceptor blocking activity, which may account, at least in part, for atropine flush.