Tubulovascular nitric oxide crosstalk - Buffering of angiotensin II-induced medullary vasoconstriction
Tubulovascular nitric oxide crosstalk - Buffering of angiotensin II-induced medullary vasoconstriction
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DOI：
10.1161/01.res.0000035243.66189.92
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发表时间：
2002-09-20
影响因子：
20.1
通讯作者：
Cowley, AW
中科院分区：
文献类型：
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作者：
Dickhout, JG;Mori, T;Cowley, AW
研究旨在确定血管紧张素II(Ang II)介导的肾髓质血流量减少的缓冲作用的NO来源。用Fura-2-AM和4，5-二氨基荧光素二乙酸酯(DAF-2DA)分别测定直肠血管周细胞和内皮细胞内钙离子浓度([Ca~(2+)](1))和一氧化氮([NO](1))的含量。通过用乳胶微球灌流破坏直肠血管内皮细胞，可以对周细胞进行成像。血管紧邻粗大升支时，Ang II(1Mumol/L)可使直肠血管周细胞[NO](1)增加19+/-6U。无mTALs的离体直血管周细胞[Ca~(2+)](1)迅速升高，峰值为248+/-107nmol/L，持续升高至107+/-75nmol/L，但对AngⅡ(I mumol/L)和钙离子载体4-bromo-A23187(5mumol/L)均无明显升高。这些观察结果表明，直肠血管周细胞中缺少Ang II和钙敏感性NO的产生。在内皮完整的离体直血管中，Ang II使[Ca~(2+)]从128+/-28降至62+/-13nmol/L，但不能升高[NO](1)。然而，钙离子载体确实增加了内皮细胞(47+/-8U)中的[NO](1)，表明存在钙敏感的NO产生。Ang II(33+/-6 U)和Ca~(2+)离子载体(51+/-18 U)均可使单个mTALs[NO]显著升高。我们的结论是，Ang II作为收缩作用的一部分，增加了直肠血管降支周细胞内的[Ca~(2+)](1)，这种血管收缩作用被周围小管元件(如mTALs)产生的NO缓冲。
Studies were designed to determine the source of NO responsible for buffering of the angiotensin II (Ang II)-mediated decrease of blood flow in the renal medulla. Intracellular Ca2+ concentration ([Ca2+](1)) and NO production ([NO](1)) of pericytes and endothelium of the vasa recta were independently measured with the use of fura 2-AM and 4,5-diaminofluorescein diacetate (DAF-2DA), respectively, in microtissue strips of the vascular bundles of the outer medullary vasa recta. Disruption of the endothelium of the vasa recta by perfusion with latex microspheres enabled imaging of the pericytes. Ang II (1 mumol/L) produced an increase of [NO](1) of 19 +/- 6 U in pericytes of the vasa recta when the vessels were adjacent to medullary thick ascending limbs (mTALs). Pericytes of isolated vasa recta without surrounding mTALs showed a rapid peak increase in [Ca2+](1) of 248 +/- 107 nmol/L, with a sustained elevation of 107 +/- 75 nmol/L, but did not show an increase in [NO](1) to either Ang II (I mumol/L) or the Ca2+ ionophore 4-bromo-A23187 (5 mumol/L). These observations indicated the lack of Ang II and Ca2+-sensitive NO production in pericytes of the vasa recta. In isolated vasa recta with intact endothelium, Ang II reduced [Ca2+], from 128 +/- 28 to 62 +/- 13 nmol/L and failed to increase [NO](1). However, the Ca2+ ionophore did increase [NO](1) in the endothelium (47 +/- 8 U), indicating the presence of Ca2+-sensitive NO production. Significant increases of [NO], were observed in single isolated mTALs in response to both Ang II (33 +/- 6 U) and the Ca2+ ionophore (51 +/- 18 U). We conclude that Ang II increases [Ca2+](1) in pericytes of the descending vasa recta as part of its constrictor action and that this vasoconstriction is buffered by the NO from the surrounding tubular elements, such as mTALs.