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

Abstract

We have previously demonstrated that long-term administration of doxazosin, an α 1-adrenoceptor (α 1-AR) antagonist, causes an up-regulation in the expression of α 1-AR subtype mRNAs in the rat genitourinary tract and suggested that these changes may affect long-term effectiveness of α 1-AR antagonists when used to treat the lower urinary tract symptoms of benign prostatic hyperplasia. As chronic administration of α 1-AR antagonists may cause similar alterations in other tissues in which α 1-ARs play a physiologic role, we examined the effects of long-term administration of doxazosin on the expression of α 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. α 1A, α 1B and α 1D-AR mRNA expression levels were quantified by real-time reverse transcription polymerase chain reaction. The rank order of expression levels of the α 1-AR mRNAs in rat tissues were: α 1A-AR, kidney > heart > aorta; α 1B-AR, heart > kidney > aorta; α 1D-AR, aorta > kidney = heart. Chronic administration of doxazosin caused an up-regulation in the mRNA level of α 1A, α 1B and α 1D-ARs in the rat kidney, heart and aorta, respectively. Our data demonstrate that doxazosin treatment causes differential alterations in the expression of α 1-AR subtype mRNAs in different rat tissues. These findings may provide insight into the long-term effects of α 1-AR antagonists in the treatment of diseases involving tissues whose function is regulated by α 1-ARs.