Renal and cardiac neuropeptide Y and NPY receptors in a rat model of congestive heart failure
Renal and cardiac neuropeptide Y and NPY receptors in a rat model of congestive heart failure
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DOI：
10.1152/ajprenal.00191.2007
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发表时间：
2007-12-01
影响因子：
4.2
通讯作者：
Zukowska, Zofia
中科院分区：
文献类型：
--
作者：
Callanan, Ean Y.;Lee, Edward W.;Zukowska, Zofia
神经肽Y（NPY）与去甲肾上腺素共同释放，并通过Y1受体（R）刺激血管收缩、血管和心肌细胞肥大，并通过Y2 R刺激血管生成。尽管心力衰竭时循环中的神经肽Y升高，但神经肽Y的作用仍不清楚。在Wistar大鼠高输出量心力衰竭的下腔静脉（A-V）瘘模型中测定了NPY系统的激活。在动静脉瘘动物中血浆NPY水平升高（115.7 +/- 15.3对假手术中的63.1 +/- 17.4 pM，P < 0.04）。动物要么代偿[尿Na+排泄恢复正常伴中度疾病（COMP）]，要么保持失代偿伴重度心脏和肾脏衰竭（尿Na+排泄< 0.5 meq/天）、心脏重量增加、平均动脉压和肾血流量（RBF）降低以及5-7天内死亡（DECOMP）。心脏和肾脏组织NPY随着心力衰竭而降低，与肾脏并发症的严重程度成比例。心力衰竭大鼠心、肾Y1 R mRNA表达也明显降低（1.5倍，P < 0.005）。相比之下，Y2 R表达在心脏中增加了72倍，在肾脏中增加了5.7倍（P < 0.001），与心力衰竭和心脏肥大的严重程度成比例。由于Y1 R激动剂[Leu 31，Pro34]-NPY对RBF没有影响，而Y2 R激动剂（13 - 36）-NPY增加RBF以补偿疾病，因此证实了受体表达的变化。因此，在该心力衰竭模型中，心脏和肾脏NPY Y1受体减少，Y2受体增加，表明NPY对参与心脏重塑和血管生成的受体的作用增加，并突出了NPY在充血性心力衰竭中的重要调节作用。
Neuropeptide Y (NPY) is coreleased with norepinephrine and stimulates vasoconstriction, vascular and cardiomyocyte hypertrophy via Y1 receptors (R) and angiogenesis via Y2R. Although circulating NPY is elevated in heart failure, NPY's role remains unclear. Activation of the NPY system was determined in Wistar rats with the aortocaval (A-V) fistula model of high-output heart failure. Plasma NPY levels were elevated in A-V fistula animals (115.7 +/- 15.3 vs. 63.1 +/- 17.4 pM in sham, P < 0.04). Animals either compensated [urinary Na+ excretion returning to normal with moderate disease (COMP)] or remained decompensated with severe cardiac and renal failure (urinary Na+ excretion < 0.5 meq/day), increased heart weight, decreased mean arterial pressure and renal blood flow (RBF), and death within 5-7 days (DECOMP). Cardiac and renal tissue NPY decreased with heart failure, proportionate to the severity of renal complications. Cardiac and renal Y1R mRNA expression also decreased (1.5-fold, P < 0.005) in rats with heart failure. In contrast, Y2R expression increased up to 72-fold in the heart and 5.7-fold in the kidney (P < 0.001) proportionate to severity of heart failure and cardiac hypertrophy. Changes in receptor expression were confirmed since the Y1R agonist, [Leu31, Pro34]-NPY, had no effect on RBF, whereas the Y2R agonist (13 - 36)-NPY increased RBF to compensate for disease. Thus, in this model of heart failure, cardiac and renal NPY Y1 receptors decrease and Y2 receptors increase, suggesting an increased effect of NPY on the receptors involved in cardiac remodeling and angiogenesis, and highlighting an important regulatory role of NPY in congestive heart failure.