Expression of cardiac angiotensin II AT1 receptor genes in rat hearts is regulated by steroids but not by angiotensin II
Expression of cardiac angiotensin II AT1 receptor genes in rat hearts is regulated by steroids but not by angiotensin II
复制标题
大鼠心脏中心脏血管紧张素II AT1受体基因的表达受类固醇调节，但不受血管紧张素II调节
作者：
R. Bruna;Stefan Ries;Carola Himmelstoss;A. Kurtz
目的：探讨血管紧张素II和类固醇对大鼠心脏血管紧张素II AT1a和AT1b受体基因表达的调节作用。方法：通过单侧 0.2 mm 肾动脉夹或皮下输注呋塞米（12 mg/天）和低钠饮食可增加大鼠血管紧张素 II 的内源水平。为了抑制内源性血管紧张素 II 作用，大鼠接受 AT1 受体拮抗剂氯沙坦（每天 40 毫克/公斤）或血管紧张素转换酶抑制剂雷米普利（每天 8 毫克/公斤）。皮下注射地塞米松（每天 400 μg/kg）可提高糖皮质激素的循环水平，皮下注射醋酸脱氧皮质酮（每天 2 mg/kg）可提高盐皮质激素的水平。 AT1a 和 AT1b 信使 RNA (mRNA) 水平通过逆转录酶聚合酶链反应进行半定量，并与肌动蛋白 mRNA 相关。结果：未治疗大鼠心脏中AT1a mRNA：AT1b mRNA比例为10：1。单侧肾动脉夹闭导致AT1a mRNA下降30%，而呋塞米、氯沙坦或雷米普利治疗对AT1a或AT1b mRNA水平没有影响。低钠饮食喂养的老鼠 AT1a 基因表达增加了 37%。地塞米松使 AT1a mRNA 增加 100%，AT1b mRNA 增加 300%，而醋酸脱氧皮质酮治疗使 AT1a mRNA 水平降低至对照值的 30%。结论：目前的结果表明，主要心脏 AT1a 受体基因的表达不受内源性血管紧张素 II 的反馈调节，而类固醇激素似乎是有效的调节剂，因为糖皮质激素刺激 AT1 受体基因表达，而盐皮质激素则抑制它。
Objective: To examine the regulation by angiotensin II and by steroids of the expression of the angiotensin II AT1a and AT1b receptor genes in rat hearts. Methods: Endogenous levels of angiotensin II in the rats were increased either by unilateral 0.2-mm renal artery clips or by subcutaneous infusions of frusemide (12 mg/day) and by low-sodium diet. To inhibit endogenous angiotensin II actions the rats received the AT1 receptor antagonist losartan (40 mg/kg per day) or the angiotensin converting enzyme inhibitor ramipril (8 mg/kg per day). Circulating levels of glucocorticoids were elevated by subcutaneous injections of dexamethasone (400 μg/kg per day) and levels of mineralocorticoids were increased by subcutaneous injections of deoxycorticosterone acetate (2 mg/kg per day). AT1a and AT1b messenger RNA (mRNA) levels were semiquantified by reverse-transcriptase polymerase chain reaction and related to actin mRNA. Results: The AT1a mRNA: AT1b mRNA ratio in the hearts of untreated rats was 10: 1. Unilateral renal artery clipping led to a 30% decrease in AT1a mRNA, whereas treatment with frusemide, losartan or ramipril had no effect on the AT1a or AT1b mRNA levels. Rats fed a low-sodium diet showed a 37% increase in AT1a gene expression. Dexamethasone increased AT1a mRNA by 100% and AT1b mRNA by 300%, whereas deoxycorticosterone acetate treatment decreased AT1a mRNA levels to 30% of the control values. Conclusions: The present results suggest that the expression of the predominant cardiac AT1a receptor gene is not feedback-regulated by endogenous angiotensin II, whereas steroid hormones appear to be effective regulators, because glucocorticoids stimulate AT1 receptor gene expression and mineralocorticoids inhibit it.