Heart-Microcirculation Connection

Heart-Microcirculation Connection
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心脏-微循环连接

DOI:
10.1161/hypertensionaha.120.15772
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发表时间:
--
期刊:
影响因子:
8.3
通讯作者:
Kuhn M
Kuhn M
中科院分区:
医学1区
文献类型:
--
作者:
Špiranec Spes K;Chen W;Krebes L;Völker K;Abeßer M;Eder Negrin P;Cellini A;Nickel A;Nikolaev VO;Hofmann F;Schuh K;Schweda F;Kuhn M

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心脏 ANP(心房钠尿肽)可调节动脉血压。介导其降血压作用的机制很复杂,涉及抑制肾素-血管紧张素-醛固酮系统、增加尿钠、内皮通透性和血管舒张。 ANP 的直接血管舒张作用对血压稳态的贡献存在争议,因为 ANP 受体 GC-A(鸟苷酸环化酶-A)在血管床中的表达水平各不相同。在这里,我们发现 ANP 刺激培养的微血管周细胞中的 GC-A/环 GMP 信号传导,从而通过 cGMP 依赖性蛋白激酶 I 磷酸化肌球蛋白磷酸酶 1 的调节亚基。此外,ANP 还可阻止周细胞对内皮素-1 的钙和收缩反应以及微血管收缩。在微循环周细胞中GC-A条件性失活(敲除)的小鼠中,ANP对毛细血管前小动脉和毛细血管的血管舒张作用被完全消除。与之相一致的是,尽管这些小鼠的肾排泄功能得以保留,但血压却升高了。此外,引起心脏 ANP 释放的急性血管内容量扩张不会影响对照小鼠的血压,但会在周细胞 GC-A 敲除的同窝小鼠中引发高血压反应。我们得出的结论是,GC-A/cGMP 依赖的周细胞和微循环张力调节有助于 ANP 急性和慢性调节动脉血压。图文摘要 本文提供了图文摘要。
Cardiac ANP (atrial natriuretic peptide) moderates arterial blood pressure. The mechanisms mediating its hypotensive effects are complex and involve inhibition of the renin-angiotensin-aldosterone system, increased natriuresis, endothelial permeability, and vasodilatation. The contribution of the direct vasodilating effects of ANP to blood pressure homeostasis is controversial because variable levels of the ANP receptor, GC-A (guanylyl cyclase-A), are expressed among vascular beds. Here, we show that ANP stimulates GC-A/cyclic GMP signaling in cultured microvascular pericytes and thereby the phosphorylation of the regulatory subunit of myosin phosphatase 1 by cGMP-dependent protein kinase I. Moreover, ANP prevents the calcium and contractile responses of pericytes to endothelin-1 as well as microvascular constrictions. In mice with conditional inactivation (knock-out) of GC-A in microcirculatory pericytes, such vasodilating effects of ANP on precapillary arterioles and capillaries were fully abolished. Concordantly, these mice have increased blood pressure despite preserved renal excretory function. Furthermore, acute intravascular volume expansion, which caused release of cardiac ANP, did not affect blood pressure of control mice but provoked hypertensive reactions in pericyte GC-A knock-out littermates. We conclude that GC-A/cGMP–dependent modulation of pericytes and microcirculatory tone contributes to the acute and chronic moderation of arterial blood pressure by ANP.Graphic AbstractA graphic abstract is available for this article.
DOI: 10.1161/circulationaha.117.033383
发表时间: 2018-07-31
期刊: CIRCULATION
影响因子: 37.8
作者:
Spiranec, Katarina;Chen, Wen;Kuhn, Michaela
通讯作者: Kuhn, Michaela
鸟苷酸环化酶介导 ANP 诱导的小鼠脾血管收缩。
DOI: --
发表时间: 2003
期刊: American Journal of Physiology. Regulatory Integrative and Comparative Physiology
影响因子: --
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发表时间: 2014-02-01
期刊: NATURE PROTOCOLS
影响因子: 14.8
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ANP 对清醒狗的局部血流影响:优先胃肠道血管收缩。
DOI: --
发表时间: 1991
影响因子: --
作者:
R. Woods;J. Smolich
通讯作者: J. Smolich
非甾体抗炎药通过周细胞改变直肠血管直径。
DOI: --
发表时间: 2015
期刊: AJP - Renal Physiology
影响因子: --
作者:
T. Kennedy;C. Crawford;S. Wildman;C. Peppiatt
通讯作者: C. Peppiatt