Doxazosin treatment causes differential alterations of alpha(1)-adrenoceptor subtypes in the rat kidney, heart and aorta

摘要

We have previously demonstrated that long-term administration of doxazosin, an alpha(1)-adrenoceptor (alpha(1)-AR) antagonist, causes an up-regulation in the expression of alpha(1)-AR subtype mRNAs in the rat genitourinary tract and suggested that these changes may affect long-term effectiveness of alpha(1)-AR antagonists when used to treat the lower urinary tract symptoms of benign prostatic hyperplasia. As chronic administration of alpha(1)-AR antagonists may cause similar alterations in other tissues in which alpha(1)-ARs play a physiologic role, we examined the effects of long-term administration of doxazosin on the expression of alpha(1)-AR. subtype mRNAs in several rat tissues. Rats were treated with doxazosin (4 mg/kg/day subcutaneously, supplemented with 4 mg/kg/day orally) for 12 weeks. The cDNA was prepared by reverse transcription of RNA extracted from the rat kidney, heart and aorta. alpha(1A),alpha(1B) and alpha(1D)-AR mRNA expression levels were quantified by real-time reverse transcription polymerase chain reaction. The rank order of expression levels of the alpha(1)-AR mRNAs in rat tissues were: alpha(1A)-AR, kidney > heart > aorta; alpha(1B)-AR, heart > kidney > aorta; alpha(1D)-AR, aorta > kidney = heart. Chronic administration of doxazosin caused an up-regulation in the mRNA level of alpha(1A), alpha(1B) and alpha(1D)-ARs in the rat kidney, heart and aorta, respectively. Our data demonstrate that doxazosin treatment causes differential alterations in the expression of alpha(1)-AR subtype mRNAs in different rat tissues. These findings may provide insight into the long-term effects of alpha(1)-AR antagonists in the treatment of diseases involving tissues whose function is regulated by alpha(1)-ARs. (C) 2004 Elsevier Inc. All rights reserved.