Long-term endothelin receptor antagonist administration improves alterations in expression of various cardiac genes in failing myocardium of rats with heart failure.
Long-term endothelin receptor antagonist administration improves alterations in expression of various cardiac genes in failing myocardium of rats with heart failure.
复制标题
长期给予内皮素受体拮抗剂可改善心力衰竭大鼠衰竭心肌中各种心脏基因表达的变化。
作者：
S. Sakai;Takashi Miyauchi;I. Yamaguchi
背景
我们报道了内皮素（ET）A型（ET（A））受体拮抗剂BQ-123的长期（3个月）治疗显著改善慢性心力衰竭（CHF）大鼠的生存率。然而，目前尚不清楚是否长期治疗与ET受体拮抗剂改善心脏基因表达的变化在衰竭的心脏。
方法和结果
CHF大鼠和对照假手术大鼠用BQ-123、SB 209670（ET（A/B）双受体拮抗剂）或盐水（载体）治疗3个月。BQ-123或SB 209670治疗组中CHF大鼠的存活率显著高于盐水治疗组。BQ-123或SB 209670治疗CHF大鼠可显著抑制心力衰竭经典分子标志物（心房利钠肽和β-肌球蛋白重链的mRNA水平）基因表达的变化。长期BQ-123治疗还使衰竭心脏中功能性分子标志物表达的改变正常化（例如，兰尼碱受体、肌浆网Ca（2+）-ATP酶、血管紧张素转换酶、血管紧张素II 1型受体和前原ET-1的mRNA水平）。
结论
我们首次证明了ET受体拮抗剂的长期（3个月）治疗改善了经典分子标记物的各种心脏基因表达的改变。（例如，心房利钠肽和β-肌球蛋白重链中的mRNA）和功能性分子标志物（例如，Ryanodine受体、肌浆网Ca（2+）-ATP酶、血管紧张素转换酶、血管紧张素II 1型受体、和prepro-ET-1），提示ET阻断剂对CHF大鼠存活率的显著改善部分归因于对衰竭心脏中分子变化的预防。
BACKGROUND
We reported that long-term (3-month) treatment with the endothelin (ET) type A (ET(A)) receptor antagonist BQ-123 markedly improved survival in rats with chronic heart failure (CHF). However, it is not known whether long-term treatment with an ET receptor antagonist improves alterations in the expression of cardiac genes in failing hearts.
METHODS AND RESULTS
CHF rats and control sham-operated rats were treated with BQ-123, SB209670 (ET(A/B) dual receptor antagonist), or saline (vehicle) for 3 months. The survival of CHF rats was markedly higher in the BQ-123 or SB209670 treatment group than in the saline treatment group. The changes in the gene expression of classic molecular markers for failing hearts (mRNA levels of atrial natriuretic peptide and beta-myosin heavy chain) were greatly inhibited by BQ-123 or SB209670 treatment in CHF rats. Long-term BQ-123 treatment also normalized the alterations in the expression of functional molecular markers in failing hearts (eg, mRNA levels of ryanodine receptor, sarcoplasmic reticulum Ca(2+)-ATPase, angiotensin-converting enzyme, angiotensin II type 1 receptor, and prepro-ET-1).
CONCLUSIONS
We demonstrated for the first time that long-term (3-month) treatment with an ET receptor antagonist improves the alterations in the expression of various cardiac genes of classic molecular markers (eg, mRNA in atrial natriuretic peptide and beta-myosin heavy chain) and of functional molecular markers (eg, mRNA levels of ryanodine receptor, sarcoplasmic reticulum Ca(2+)-ATPase, angiotensin-converting enzyme, angiotensin II type 1 receptor, and prepro-ET-1) in the failing hearts of CHF rats, suggesting that the great improvement of survival in CHF rats by an ET blocker is partly attributed to the prevention of molecular changes in failing hearts.
影响因子：
20.1
作者：
L. Meggs;J. Coupet;Harer Huang;W. Cheng;Peng Li;J. Capasso;J. Homcy;P. Anversa
通讯作者：
L. Meggs;J. Coupet;Harer Huang;W. Cheng;Peng Li;J. Capasso;J. Homcy;P. Anversa