Effects of doxazosin enantiomers on α-adrenoceptors of isolated rabbit blood vessels

Doxazosin, a high selective α₁-adrenoceptor antagonist, is considered as the first-line therapy for the patients with benign prostatic hyperplasia (BPH) and also produce several side effects in cardiovascular system. In this study, we observed the isometric vasoconstrictive responses of the rabbit isolated arterial rings to electric field stimulation and noradrenaline (NA) to study the effects of R-doxazosin (R-DOX) and S-doxazosin (S-DOX) on the α₁-adrenoceptor-regulated vasoconstrictive responses in the rabbit isolated ear artery, mesenteric artery and pulmonary artery, and the effects of higher concentration of S-DOX and R-DOX on presynaptic α₂-adrenoceptor-regulated purinergic vasoconstriction in the rabbit isolated saphenous artery. We found that R-DOX and S-DOX competitively inhibited the vasoconstriction induced by NA in the rabbit isolated ear artery, mesenteric artery and pulmonary artery. The pA₂ values of R-DOX and S-DOX against NA in the rabbit isolated ear artery, mesenteric artery and pulmonary artery were 7.91±0.03 and 7.53±0.05, 7.80±0.05 and 7.29±0.07, 8.32±0.06 and 7.97±0.07, respectively. The pA₂ values of R-DOX in the three arterial preparations were significantly higher than those of S-DOX (P<0.01). R-DOX and S-DOX at the concentrations of 0.1-10 μmol·L^-1 did not affect the vasoconstriction induced by electric stimulation in the rabbit isolated saphenous artery. R-DOX and S-DOX at 100 μmol·L^-1 in the rabbit isolated saphenous artery completely inhibited the vascular responses to exogenous NA, but did not affect the vascular responses to exogenous adenosine triphosphate (1 mmol·L^-1). It is reasonable to suggest that R-DOX and S-DOX competitively inhibit the vasoconstriction induced by NA in the rabbit ear artery, mesenteric artery and pulmonary artery, and the pA₂ values of S-DOX are significantly lower than those of R-DOX. The higher concentration (10 μmol·L^-1) of R-DOX and S-DOX does not affect the presynaptic α₂-adrenoceptors at sympathetic nerve terminals of the rabbit saphenous artery.