EFFECT OF ALPHA(1)-ADRENOCEPTOR ANTAGONISTS, PRAZOSIN AND URAPIDIL, ON A FINGER SKIN VASOCONSTRICTOR RESPONSE TO COLD STIMULATION

Objectives: Cold stimulation causes a finger skin vasoconstrictor resp onse, which is regulated by stimulation of alpha-adrenergic receptors and is reduced by administration of prazosin. The purpose of this stud y was to investigate, using a laser Doppler flowmeter, whether the dec rease in the finger skin vasoconstrictor response to cold stimulation produced by administration of two different alpha(1)-adrenoceptor anta gonists, prazosin and urapidil, was correlated with the corresponding plasma drug concentration, and whether this method could be used to ev aluate the relative potency of these alpha(1)-adrenoceptor antagonists in human subjects. Method: In thirteen healthy male subjects (20-42 y ), finger tip skin blood flow was measured during cold stimulation bef ore and 1, 2, 3, 6, and 9 h after administration of placebo, prazosin (1 mg) or urapidil (60 mg). Results: Both prazosin and urapidil signif icantly decreased the vasoconstrictor response to cold stimulation. Th e degree of the decrement in the response indicated by the reduction r atio was significantly correlated with the plasma concentration of pra zosin and urapidil. The alpha(1)-adrenoceptor blocking activity of pra zosin estimated by the regression lines was about 130-times more poten t than that of urapidil. Conclusion: These findings suggest that the c old stimulation response of finger skin vasoconstriction may be used t o evaluate the relative alpha(1)-adrenoceptor blocking potency of drug s.