INFLUENCE OF REPEATED PRAZOSIN ADMINISTRATION ON CARDIOVASCULAR-RESPONSES IN RATS AND RABBITS

Prazosin was injected i.v. at a dose of 50 mu g/kg every 2 h for 8 h i n conscious rats. Its hypotensive action significantly declined. A sim ilar effect was also observed in rabbits pretreated with prazosin (40 mu g/kg, i.v.) every 1 h for 4 h. In prazosin-treated rabbits, the tot al peripheral resistance became less responsive to phentolamine stimul ation. Repeated prazosin administration abolished its ability to block receptors in a model of anococcygue muscle contraction after noradren aline (NA) stimulation. The alpha-adrenoceptors in anococcygue muscle exhibited lower pD(2) to NA and lower pA(2) to prazosin in prazosin-tr eated rats. The results demonstrate that repeated prazosin administrat ion reduces the effectiveness of alpha-adrenoceptors blockers.