Influence of repeated prazosin administration on cardiovascular responses in rats and rabbits

Prazosin was injected i.v. at a dose of 50 g/kg every 2 h for 8 h in conscious rats. Its hypotensive action significantly declined. A similar effect was also observed in rabbits pretreated with prazosin (40 g/kg, i.v.) every 1 h for 4 h. In prazosin-treated rabbits, the total peripheral resistance became less responsive to phentolamine stimulation. Repeated prazosin administration abolished its ability to block receptors in a model of anococcygue muscle contraction after noradrenaline (NA) stimulation. The -adrenoceptors in anococcygue muscle exhibited lower pD₂ to NA and lower pA₂ to prazosin in prazosin-treated rats. The results demonstrate that repeated prazosin administration reduces the effectiveness of -adrenoceptors blockers.