Laboratório de Eletrofisiologia Cardíaca Antonio Paes de Carvalho, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, CCS, Bloco G, 21.941-902, Rio de Janeiro, Brazil.
Cardiovasc Drugs Ther. 2014 Apr;28(2):125-35. doi: 10.1007/s10557-013-6503-8.
Myocardial tolerance to ischaemia/reperfusion (I/R) injury is improved by exercise training, but this cardioprotection is impaired by the chronic use of anabolic androgenic steroids (AAS). The present study evaluated whether blockade of angiotensin II receptor (AT1-R) with losartan and aldosterone receptor (mineralocorticoid receptor, MR) with spironolactone could prevent the deleterious effect of AAS on the exercise-induced cardioprotection.
Male Wistar rats were exercised and treated with either vehicle, nandrolone decanoate (10 mg/kg/week i.m.) or the same dose of nandrolone plus losartan or spironolactone (20 mg/kg/day orally) for 8 weeks. Langendorff-perfused hearts were subjected to I/R and evaluated for the postischaemic recovery of left ventricle (LV) function and infarct size. mRNA and protein expression of angiotensin II type 1 receptor (AT1-R), mineralocorticoid receptor (MR), and KATP channels were determined by reverse-transcriptase polymerase chain reaction and Western blotting. Postischaemic recovery of LV function was better and infarct size was smaller in the exercised rat hearts than in the sedentary rat hearts. Nandrolone impaired the exercise-induced cardioprotection, but this effect was prevented by losartan (AT1-R antagonist) and spironolactone (MR antagonist) treatments. Myocardial AT1-R and MR expression levels were increased, and the expression of the KATP channel subunits SUR2a and Kir6.1 was decreased and Kir6.2 increased in the nandrolone-treated rat hearts. The nandrolone-induced changes of AT1-R, MR, and KATP subunits expression was normalized by the losartan and spironolactone treatments.
The chronic nandrolone treatment impairs the exercise-induced cardioprotection against ischaemia/reperfusion injury by activating the cardiac renin-angiotensin-aldosterone system and downregulating KATP channel expression.
运动训练可提高心肌对缺血/再灌注（I/R）损伤的耐受性，但慢性使用合成代谢雄激素类固醇（AAS）会损害这种心脏保护作用。本研究评估了用氯沙坦阻断血管紧张素 II 受体（AT1-R）和用螺内酯阻断醛固酮受体（盐皮质激素受体，MR）是否可以预防 AAS 对运动诱导的心脏保护作用的有害影响。
雄性 Wistar 大鼠接受运动训练，并接受以下处理：载体、癸酸诺龙（10mg/kg/周肌内注射）或相同剂量的癸酸诺龙加氯沙坦或螺内酯（20mg/kg/天口服），共 8 周。Langendorff 灌流心脏进行 I/R，并评估左心室（LV）功能和梗塞面积的缺血后恢复情况。通过逆转录聚合酶链反应和 Western blot 测定血管紧张素 II 型 1 受体（AT1-R）、盐皮质激素受体（MR）和 KATP 通道的 mRNA 和蛋白表达。与久坐不动的大鼠心脏相比，运动大鼠心脏的 LV 功能缺血后恢复更好，梗塞面积更小。诺龙损害了运动诱导的心脏保护作用，但这种作用可被氯沙坦（AT1-R 拮抗剂）和螺内酯（MR 拮抗剂）治疗预防。心肌 AT1-R 和 MR 表达水平增加，而 KATP 通道亚基 SUR2a 和 Kir6.1 的表达减少，Kir6.2 增加在诺龙处理的大鼠心脏中。氯沙坦和螺内酯治疗使诺龙诱导的 AT1-R、MR 和 KATP 亚基表达变化正常化。
慢性诺龙处理通过激活心脏肾素-血管紧张素-醛固酮系统和下调 KATP 通道表达，损害运动诱导的缺血/再灌注损伤的心脏保护作用。
