Direct Vasoactive Effects of the Chromogranin A (CHGA) Peptide Catestatin in Humans In Vivo
Direct Vasoactive Effects of the Chromogranin A (CHGA) Peptide Catestatin in Humans In Vivo
复制标题
DOI：
10.3109/10641960903265246
复制
发表时间：
2010-01-01
影响因子：
12.3
通讯作者：
O'Connor, Daniel T.
中科院分区：
文献类型：
--
作者：
Fung, Maple M.;Salem, Rany M.;O'Connor, Daniel T.
儿茶酚素是嗜铬粒素A(ChGA)的一种生物活性多肽，与儿茶酚胺从分泌囊泡中共同释放。儿茶素可以起到血管扩张剂的作用，但在高血压时会减弱。为了在体内评价这种潜在的血管扩张剂而没有全身的反调节，我们用苯肾上腺素进行药物收缩后，向18名血压正常的男性和女性的手背静脉注入目标浓度类似于50、类似于500、类似于5000 NM的儿茶素。另一种CHGA多肽--胰抑素作为阴性对照。在预收缩至接近69%后，增加儿茶素的浓度可引起剂量依赖性的血管扩张(P=0.019)，女性受试者(接近于44%)主要表现为血管扩张。儿茶素对血管扩张的EC50(与30 nM相似)与循环内源性儿茶素的EC50(4.4 nM)相同数量级。在胰腺抑素的对照输注过程中，没有发生血管扩张。然后测定了622名无高血压的健康受试者的血浆CHGA、儿茶素及CHGA转儿茶素的过程。女性受试者的血浆儿茶素水平高于男性(P=0.001)，但CHGA前体浓度较低(P=0.006)，反映了CHGA到儿茶素的过程增加(P<；0.001)。我们的结果表明，儿茶素可以在体内扩张人体血管，特别是在女性体内。儿茶素可能导致内源性血管张力的性别差异，从而影响高血压的复杂易感性。
Catestatin is a bioactive peptide of chromogranin A (CHGA) that is co-released with catecholamines from secretory vesicles. Catestatin may function as a vasodilator and is diminished in hypertension. To evaluate this potential vasodilator in vivo without systemic counterregulation, we infused catestatin to target concentrations of similar to 50, similar to 500, similar to 5000 nM into dorsal hand veins of 18 normotensive men and women, after pharmacologic venoconstriction with phenylephrine. Pancreastatin, another CHGA peptide, was infused as a negative control. After preconstriction to similar to 69%, increasing concentrations of catestatin resulted in dose-dependent vasodilation (P = 0.019), in female subjects (to similar to 44%) predominantly. The EC50 (similar to 30 nM) for vasodilation induced by catestatin was the same order of magnitude to circulating endogenous catestatin (4.4 nM). No vasodilation occurred during the control infusion with pancreastatin. Plasma CHGA, catestatin, and CHGA-to-catestatin processing were then determined in 622 healthy subjects without hypertension. Female subjects had higher plasma catestatin levels than males (P = 0.001), yet lower CHGA precursor concentrations (P = 0.006), reflecting increased processing of CHGA-to-catestatin (P < 0.001). Our results demonstrate that catestatin dilates human blood vessels in vivo, especially in females. Catestatin may contribute to sex differences in endogenous vascular tone, thereby influencing the complex predisposition to hypertension.