Effects of Relaxin on Arterial Dilation, Remodeling, and Mechanical Properties
Effects of Relaxin on Arterial Dilation, Remodeling, and Mechanical Properties
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DOI：
10.1007/s11906-011-0231-x
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发表时间：
2011-12-01
影响因子：
5.6
通讯作者：
Shroff, Sanjeev G.
中科院分区：
文献类型：
--
作者：
Conrad, Kirk P.;Shroff, Sanjeev G.
对清醒的大鼠和人类给予松弛素可增强全身和肾脏血管舒张。分子机制根据松弛素释放的持续时间而变化-所谓的“快速”（几分钟内）或“持续”（几小时到几天）血管舒张反应-两者都是内皮依赖性的。快速反应由G（α i/o）蛋白偶联至磷酸肌醇-3激酶/Akt（蛋白激酶B）依赖性磷酸化和一氧化氮合酶的活化介导。持续的反应是由血管内皮和胎盘生长因子介导的，以及动脉明胶酶活性的增加。因此，分别在松弛素治疗数小时或数天后，动脉MMP-9或MMP-2在gly-leu键处水解“大”内皮素（ET）以形成ET 1 -32，其继而激活内皮ETB受体/一氧化氮血管舒张途径。对清醒大鼠施用松弛素还增加了全身动脉顺应性和选择的分离血管如小肾动脉（SRA）的被动顺应性。SRA被动顺应性的增加是由几何重塑（向外）和组成重塑（胶原蛋白减少）介导的。在脑实质动脉中也观察到松弛素诱导的几何重构，并且这种重构似乎是通过过氧化物酶体增殖物激活受体-γ的激活。考虑到松弛素的血管舒张和动脉重塑特性，该激素可能在异常妊娠、心力衰竭和与动脉硬化相关的病理学方面具有治疗潜力。
Administering relaxin to conscious rats and humans elicits systemic and renal vasodilation. The molecular mechanisms vary according to the duration of relaxin exposure-so-called "rapid" (within minutes) or "sustained" (hours to days) vasodilatory responses-both being endothelium-dependent. Rapid responses are mediated by G(alpha i/o) protein coupling to phosphoinositol-3 kinase/Akt (protein kinase B)-dependent phosphorylation and activation of nitric oxide synthase. Sustained responses are mediated by vascular endothelial and placental growth factors, as well as increases in arterial gelatinase activity. Thus, after hours or days of relaxin treatment, respectively, arterial MMP-9 or MMP-2 hydrolyze "big" endothelin (ET) at a gly-leu bond to form ET1-32, which in turn activates the endothelial ETB receptor/nitric oxide vasodilatory pathway. Administration of relaxin to conscious rats also increases global systemic arterial compliance and passive compliance of select isolated blood vessels such as small renal arteries (SRA). The increase in SRA passive compliance is mediated by both geometric remodeling (outward) and compositional remodeling (decreased collagen). Relaxin-induced geometric remodeling has also been observed in brain parenchymal arteries, and this remodeling appears to be via the activation of peroxisome proliferator-activated receptor-gamma. Given the vasodilatory and arterial remodeling properties of relaxin, the hormone may have therapeutic potential in the settings of abnormal pregnancies, heart failure, and pathologies associated with stiffening of arteries.