Cardiac Renin Levels Are Not Influenced by the Amount of Resident Mast Cells
Cardiac Renin Levels Are Not Influenced by the Amount of Resident Mast Cells
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DOI：
10.1161/hypertensionaha.109.133892
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发表时间：
2009-08-01
期刊：
影响因子：
8.3
通讯作者：
Danser, A. H. Jan
中科院分区：
文献类型：
--
作者：
Krop, Manne;van Veghel, Richard;Danser, A. H. Jan
为了研究肥大细胞是否在心脏中释放肾素，我们研究了这种细胞的肾素和原肾素合成，使用人肥大细胞株人肥大细胞瘤1和LAD 2，以及肥大细胞增生症患者的新鲜肥大细胞。我们还量化了肥大细胞对对照组和梗死大鼠心脏中心脏肾素水平的贡献。人肥大细胞瘤1细胞含有并释放血管紧张素I生成活性，这种活性的抑制，由肾素抑制剂阿利吉仑是相当的重组人肾素。胰蛋白酶激活的原肾素增加血管紧张素I生成活性的介质中，只，这表明释放，但不存储的原肾素。腺苷酸环化酶激活剂毛喉素、cAMP类似物8-db-cAMP和去甲肾上腺素化合物48/80增加了肾素释放而不影响原肾素。血管紧张素II阻断了毛喉素诱导的肾素释放。在LAD 2细胞和新鲜肥大细胞中未检测到血管紧张素I产生活性。非灌注大鼠心脏含有血管紧张素I生成活性，阿利吉仑阻断了约70%的这种活性。30分钟的缓冲液灌注冲走了>70%的阿利吉仑耐受的血管紧张素I生成活性。延长的缓冲液灌注或化合物48/80没有进一步降低心脏血管紧张素I生成活性或诱导灌注缓冲液中血管紧张素I生成活性释放。在梗塞心脏中的结果是相同的，尽管在这样的心脏中肥大细胞数量增加。总之，人肥大细胞瘤1细胞释放肾素和原肾素，这种释放的调节类似于肾肾素。然而，这并不是所有肥大细胞的统一性质。在正常和病理生理条件下，肥大细胞似乎都不是心脏中肾素的来源。（高血压。2009; 54：315-321）。
To investigate whether mast cells release renin in the heart, we studied renin and prorenin synthesis by such cells, using the human mast cell lines human mastocytoma 1 and LAD2, as well as fresh mast cells from mastocytosis patients. We also quantified the contribution of mast cells to cardiac renin levels in control and infarcted rat hearts. Human mastocytoma 1 cells contained and released angiotensin I-generating activity, and the inhibition of this activity by the renin inhibitor aliskiren was comparable to that of recombinant human renin. Prorenin activation with trypsin increased angiotensin I-generating activity in the medium only, suggesting release but not storage of prorenin. The adenylyl cyclase activator forskolin, the cAMP analogue 8-db-cAMP, and the degranulator compound 48/80 increased renin release without affecting prorenin. Angiotensin II blocked the forskolin-induced renin release. Angiotensin I-generating activity was undetectable in LAD2 cells and fresh mast cells. Nonperfused rat hearts contained angiotensin I-generating activity, and aliskiren blocked approximate to 70% of this activity. A 30-minute buffer perfusion washed away >70% of the aliskiren-inhibitable angiotensin I-generating activity. Prolonged buffer perfusion or compound 48/80 did not decrease cardiac angiotensin I-generating activity further or induce angiotensin I- generating activity release in the perfusion buffer. Results in infarcted hearts were identical, despite the increased mast cell number in such hearts. In conclusion, human mastocytoma 1 cells release renin and prorenin, and the regulation of this release resembles that of renal renin. However, this is not a uniform property of all mast cells. Mast cells appear an unlikely source of renin in the heart, both under normal and pathophysiological conditions. (Hypertension. 2009; 54: 315-321.)