Microvascular effects of aldosterone and angiotensin type 2 receptors.
Microvascular effects of aldosterone and angiotensin type 2 receptors.
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醛固酮和血管紧张素 2 型受体的微血管作用。
DOI：
10.1161/01.hyp.0000161868.75872.e6
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Pallone,ThomasL
中科院分区：
文献类型：
--
作者：
Pallone,ThomasL
在高血压的最新一期中，Gonzalez等人描述了醛固酮对肠系膜血管紧张素2型受体（AT2R）表达的调节。1主要结果如下：（1）AT_2R激活使苯肾上腺素预收缩的肠系膜小动脉扩张，（2）口服盐负荷4天消除了AT_2R介导的扩张，并降低了AT_2R mRNA和蛋白的表达，（3）由于盐负荷的作用与肾上腺切除相似，因此涉及肾上腺激素。（4）在候选肾上腺激素中，确定了醛固酮，因为盐皮质激素替代可以防止肾上腺切除术的影响;（5）醛固酮上调肠系膜小动脉血管紧张素Ⅱ受体（AT2R）的表达。这些精心设计的一系列实验强烈支持醛固酮刺激AT2R表达的作用，并增加了醛固酮在血管生理学中发挥的日益重要的作用。Gonzalez等1观察到的AT2R介导的血管舒张作用完美地再现了肠系膜和其他血管制备物中报告的类似效应。2-5 AT2R诱导的肠系膜小动脉血管舒张表现为内皮依赖性，6通过激肽和一氧化氮（NO）产生发挥作用，7并通过刺激大电导Ca2+依赖性钾通道涉及肌细胞超极化。[8]这种AT2R介导的血管阻力的降低普遍存在于肠系膜血管床之外。通过输注血管紧张素II加AT1受体阻滞剂全身性AT2R激活可降低血压9，AT2缺失小鼠具有轻度高血压，对醋酸脱氧皮质酮加盐的血压反应过度。10、11颈动脉、12冠状动脉、13肾传入小动脉、14 - 16和直降血管17通过AT2R激活而扩张。缓激肽B2受体激活和NO生成参与AT2R介导的血管舒张是一个共同的发现，但它是不统一的，在所有的实验准备。破坏缓激肽B2受体不能消除AT2R刺激的cGMP和NO在小鼠肾脏中的产生。18肾传入小动脉中的AT2R激活可能在很大程度上与血管舒张性细胞色素P450表氧化酶产物的产生有关，而不是NO.15在下行直小血管中，AT2R激活通过促进内皮细胞质Ca 2+反应来舒张血管，否则该反应会被AT 1受体刺激抑制。在该制剂中，AT2R活化通过抑制活性氧的产生来增加NO的生物利用度。[17，19]总之，冈萨雷斯等人1关于AT2 R激活具有血管舒张作用的发现在很大程度上支持了先前的观察结果。醛固酮调节肠系膜小动脉中AT2R转录的能力是新的，并且增加了越来越多的文献，证明盐皮质激素的直接微循环作用。醛固酮因其刺激肾脏远端钠重吸收的能力而被广泛认可，这一过程部分通过增加远端小管和集合管中转运蛋白的表达而发生。当配体结合的盐皮质激素受体移位到细胞核并刺激转录时，就会发生“基因组效应”。除了在肾脏中的长期调节外，已发现醛固酮具有收缩和扩张微血管的"非基因组"效应。这种对血管系统的急性影响已经被认识了一段时间20，并已成为最近机制研究的主题。在NO合酶抑制剂存在下，醛固酮促进苯肾上腺素减少人前臂的血流量。21、一份关于…
In the current issue of Hypertension, Gonzalez et al describe the modulation of mesenteric vascular angiotensin type 2 receptor (AT2R) expression by aldosterone. 1 The principal findings are as follows:(1) AT2R activation dilates phenylephrine preconstricted mesenteric arterioles;(2) 4 days of oral salt loading eliminates AT2R-mediated dilation and reduces expression of AT2R mRNA and protein;(3) an adrenal hormone is implicated because the effects of salt loading are mimicked by adrenalectomy;(4) of the candidate adrenal hormones, aldosterone is identified because mineralocorticoid replacement prevents the effects of adrenalectomy; and (5) aldosterone upregulates AT2R expression in explanted mesenteric arterioles. These well designed series of experiments strongly support a role for aldosterone to stimulate expression of AT2R and adds to the growing repertoire of roles that aldosterone plays in vasculature physiology. The AT2R-mediated vasodilation observed by Gonzalez et al1 elegantly reproduces similar effects reported in the mesentery and other vascular preparations. 2–5 AT2R induced vasodilation of mesenteric arterioles appears as endotheliumdependent, 6 acts through kinin and nitric oxide (NO) generation, 7 and involves myocyte hyperpolarization through stimulation of large-conductance Ca2+-dependent potassium channels. 8 Such AT2R-mediated reduction of vascular resistance generalizes beyond the mesenteric vascular bed. Systemic AT2R activation through infusion of angiotensin II plus AT1 receptor blockers lowers blood pressure9 and AT2-null mice have mild hypertension with an exaggerated blood pressure response to deoxycorticosterone acetate plus salt. 10, 11 Carotid arteries, 12 coronary arterioles, 13 renal afferent arterioles, 14–16 and descending vasa recta17 are dilated by AT2R activation. The participation of bradykinin B2 receptor activation and NO generation in AT2R-mediated vasodilation is a common finding but it is not uniform in all experimental preparations. Disruption of bradykinin B2 receptor fails to eliminate AT2R-stimulated cGMP and NO generation in the murine kidney. 18 AT2R activation in the renal afferent arteriole may be largely tied to generation of vasodilatory cytochrome P450 epoxygenase products rather than NO. 15 In descending vasa recta, AT2R activation vasodilates by facilitating endothelial cytoplasmic Ca2+ responses that are otherwise inhibited by AT1 receptor stimulation. In that preparation, AT2R activation increases NO bioavailability by inhibiting generation of reactive oxygen species. 17, 19 Taken together, the finding by Gonzales et al1 that AT2R activation is vasodilatory largely supports previous observations. The ability of aldosterone to regulate AT2R transcription in mesenteric arterioles1 is novel and adds to a growing literature that demonstrates direct microcirculatory effects of mineralocorticoids. Aldosterone is well recognized for its ability to stimulate distal sodium reabsorption in the kidney, a process that partially occurs through increased expression of transporters in distal tubule and collecting duct. That “genomic effect” takes place when ligand-bound mineralocorticoid receptor translocates to the nucleus and stimulates transcription. In addition to long-term regulation in the kidney, aldosterone has been found to have “nongenomic” effects to constrict and dilate microvessels. Such acute effects on the vasculature have been recognized for some time20 and have become the subject of recent mechanistic investigations. In the presence of NO synthase inhibition, aldosterone facilitates blood flow reduction to the human forearm by phenylephrine. 21 A report of …
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醛固酮的许多靶标。
影响因子：
8.3
作者：
E. Schiffrin
通讯作者：
E. Schiffrin
高盐饮食抑制阻力动脉中2型血管紧张素受体的表达
影响因子：
8.3
作者：
Magdalena González;L. Lobos;F. Castillo;L. Galleguillos;Nandy C Lopez;L. Michea
通讯作者：
L. Michea
DOI：
10.1046/j.1365-201x.2000.00638.x
发表时间：
2000-01-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
Kohagura, K;Endo, Y;Ito, S
通讯作者：
Ito, S
影响因子：
19.6
作者：
L. Navar
通讯作者：
L. Navar
PKC 和活性氧在直肠血管周细胞中的 ANG II 信号传导。
DOI：
10.1152/ajpheart.01135.2003
发表时间：
2004
期刊：
American journal of physiology. Heart and circulatory physiology
影响因子：
--
作者：
Zhang,Zhong;Rhinehart,Kristie;Kwon,Whaseon;Weinman,Edward;Pallone,ThomasL
通讯作者：
Pallone,ThomasL