Testosterone-induced relaxation of rat aorta is androgen structure specific and involves K+ channel activation

被引:102
作者
Ding, AQ
Stallone, JN [1 ]
机构
[1] Texas A&M Univ, Coll Vet Med, Dept Vet Physiol & Pharmacol, College Stn, TX 77843 USA
[2] Texas A&M Univ, Michael E De Bakey Inst Comparat Cardiovasc Sci, College Stn, TX 77843 USA
关键词
endothelium; endothelium-dependent vasodilation; endothelium-independent; vasodilation; vasorelaxation;
D O I
10.1152/jappl.2001.91.6.2742
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Recent studies have established that testosterone (Tes) produces acute (nongenomic) vasorelaxation. This study examined the structural specificity of Tes-induced vasorelaxation and the role of vascular smooth muscle (VSM) K+ channels in rat thoracic aorta. Aortic rings from male Sprague-Dawley rats with (Endo+) and without endothelium (Endo-) were prepared for isometric tension recording. In Endo - aortas precontracted with phenylephrine, 5-300 muM Tes produced dose-dependent relaxation from 10 muM (4 +/- 1%) to 300 muM (100 +/- 1%). In paired Endo+ and Endo- aortas, Tes-induced vasorelaxation was slightly but significantly greater in Endo+ aortas (at 5-150 muM Tes); sensitivity (EC50) of the aorta to Tes was reduced by nearly one-half in Endo - vessels. Based on the sensitivity (EC50) of Endo- aortas, Tes, the active metabolite 5 alpha -dihydrotestosterone, the major excretory metabolites androsterone and etiocholanolone, the nonpolar esters Tes-enanthate and Tes-hemisuccinate (THS), and THS conjugates to BSA (THS-BSA) exhibited relative potencies for vasorelaxation dramatically different from androgen receptor-mediated effects observed in reproductive tissues, with a rank order of THS-BSA > Tes > androsterone = THS = etiocholanolone > dihydrotestosterone >> Tes-enanthate. Pretreatment of aortas with 5 mM 4-aminopyridine attenuated Tes-induced vasorelaxation by an average of 44 +/- 2% (25-300 muM Tes). In contrast, pretreatment of aortas with other K+ channel inhibitors had no effect. These data reveal that Tes-induced vasorelaxation is a structurally specific effect of the androgen molecule, which is enhanced in more polar analogs that have a lower permeability to the VSM cell membrane, and that the effect of Tes involves activation of K+ efflux through K+ channels in VSM, perhaps via the voltage-dependent (delayed-rectifier) K+ channel.
引用
收藏
页码:2742 / 2750
页数:9
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