Endothelin-1 is involved in stretch-induced early activation of B-type natriuretic peptide gene expression in atrial but not in ventricular myocytes - Acute effects of mixed ETA/ETB and AT(1) receptor antagonists in vivo and in vitro
Endothelin-1 is involved in stretch-induced early activation of B-type natriuretic peptide gene expression in atrial but not in ventricular myocytes - Acute effects of mixed ETA/ETB and AT(1) receptor antagonists in vivo and in vitro
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DOI：
10.1161/01.cir.96.9.3053
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发表时间：
1997-11-04
期刊：
影响因子：
37.8
通讯作者：
Ruskoaho, H
中科院分区：
文献类型：
--
作者：
Magga, J;Vuolteenaho, O;Ruskoaho, H
背景 旁分泌和自分泌因子在机械负荷诱导的心脏基因表达激活中的确切作用尚不清楚。在这里，我们报道了内皮素-1 (ET-1) 和血管紧张素 II (Ang II) 受体拮抗剂对自发性高血压大鼠 (SHR) 体内急性压力超负荷诱导的心脏 B 型钠尿肽 (BNP) 基因表达激活以及体外机械拉伸诱导的心房 BNP 基因表达增加的影响。方法和结果通过输注精氨酸 (8)-加压素在清醒的 SHR 中产生急性压力超负荷(0.05μg.kg(-1).min(-1))持续2小时导致左心室和心房中BNP mRNA水平增加。推注波生坦（混合 ETA/ETB 受体拮抗剂，10 mg/kg IV）而非氯沙坦（AT(1) 受体拮抗剂，10 mg/kg IV）可阻断左心房压力超负荷产生的 BNP mRNA 水平的增加，而输注媒介物、氯沙坦和波生坦的 SHR 左心室中 BNP mRNA 水平的升高相似（增加 1.9 倍）。在离体灌注大鼠心脏制剂中，输注波生坦（1 μmol/L）2小时可抑制机械牵张引起的右心房BNP mRNA水平的增加，而AT（1）受体拮抗剂CV-11974（10 nmol/L）则没有效果。 结论 本研究的结果表明，Ang II和ET-1并不是牵张触发心室BNP基因表达增加所必需的。体内的肌细胞。相反，心房肌细胞上的机械负荷确实启动了 BNP 基因的 ET-1 依赖性表达，表明内源性 ET-1 的产生差异性地调节心房和心室肌细胞中的 BNP 基因表达。
Background The precise role of paracrine and autocrine factors in mechanical load-induced activation of cardiac gene expression is unknown. Here we report the effects of endothelin-1 (ET-1) and angiotensin II (Ang II) receptor antagonism on acute pressure overload-induced activation of cardiac B-type natriuretic peptide (BNP) gene expression in spontaneously hypertensive rats (SHRs) in vivo and on mechanical stretch-induced increase in atrial BNP gene expression it vitro.Methods and Results Acute pressure overload produced in conscious SHRs by infusion of arginine(8)-vasopressin (0.05 mu g . kg(-1) . min(-1)) for 2 hours resulted in an increase in BNP mRNA levels in the left ventricle as well as in the atrium. Bolus injections of bosentan (mixed ETA/ETB receptor antagonist, 10 mg/kg IV) but not losartan (AT(1) receptor antagonist, 10 mg/kg IV) blocked the increase of the BNP mRNA levels produced by pressure overload in the left atria, whereas the elevation of BNP mRNA levels was similar (a 1.9-fold increase) in the left ventricles of vehicle-, losartan-, and bosentan-infused SHRs. In an isolated perfused rat heart preparation, infusion of bosentan (1 mu mol/L) for 2 hours inhibited the mechanical stretch-induced increase in BNP mRNA levels in the right atria, whereas an AT(1) receptor antagonist, CV-11974 (10 nmol/L), had no effect.Conclusions The findings of the present study demonstrate that Ang II and ET-1 are not obligatorily required for stretch to trigger the increased BNP gene expression in ventricular myocytes invivo. In contrast, mechanical load on the atrial myocytes did initiate an ET-1-dependent expression of BNP gene showing that endogenous ET-1 production differentially regulates BNP gene expression in atrial and ventricular myocytes.