大鼠对哌唑嗪的快速耐受性及其机理

Tachyphylaxis and its mechanism to prazosin in rats

目的：观察大鼠对哌唑嗪的快速耐受性，并探讨其机制。

To investigate prazosin-induced tachyphylaxis and its mechanism in rats. Methods: An animal model of tachyphylaxis had been developed in which tissue or membrane receptor desensitization was established by repeated administration of prazosin. Results: A decreasing trend in sensitivity to prazosin induced hypotensive effect was derived by giving the drug intravenously four times at the same dosage of 50μg/kg to conscious rats(n=24). The α-adrenergic receptor in the anococcygeal muscle and aorta in the prazosin-induced tachyphylaxis rats exhibited a low pD2 to nore-pinephrine and pA2 to prazosin. Similarly, the receptors in brain, heart and spleen exhibited a larger kD value, indicating a low apparent affinity to [3H]prazosin. In contrast, the Emax to norepinephrine and Bmax to [3H ] prazosin was not signif-icantly changed after repeated treatment. Conclusion: The temporally reduced affinity of alpha receptors may play a ma jor role in process leading to tachyphylaixs induced by prazosin in rats.