A vasoconstrictor response to COX-1-mediated prostacyclin synthesis in young rat renal arteries that increases in prehypertensive conditions.

A vasoconstrictor response to COX-1-mediated prostacyclin synthesis in young rat renal arteries that increases in prehypertensive conditions.
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幼鼠肾动脉中对 COX-1 介导的前列环素合成的血管收缩反应在高血压前期条件下会增加。

DOI:
10.1152/ajpheart.00150.2015
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发表时间:
2015-07
期刊:
Am J Physiol Heart Circ Physiol
影响因子:
--
通讯作者:
Zhou Y
Zhou Y
中科院分区:
其他
文献类型:
--
作者:
Liu D;Liu B;Luo W;Li H;Zhang Y;Zhou Y

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本研究旨在确定前列环素(PGI 2)是否在年轻大鼠肾动脉中作为内皮源性收缩因子(EDCF)发挥作用,如果是这样,我们想研究潜在的机制以及它在高血压前期条件下如何变化。本研究分离了25-28日龄的Wistar-Kyoto(WKY)和高血压前期自发性高血压大鼠(SHR)的血管进行功能和生化分析。结果表明,在抑制NO合酶(NOS)后,PGI_2和血栓素-前列腺素(TP)受体激动剂U-46619可引起幼年WKY肾动脉收缩,其收缩程度与高血压前SHR相似。同时,内皮毒蕈碱受体激动剂ACh在NOS抑制条件下引起内皮依赖性收缩,并产生PGI 2代谢产物6-keto-PGF 1 α;两者对环氧化酶(考克斯)和/或考克斯-1抑制敏感,但在高血压前期SHR中高于年轻WKY。有趣的是,在WKY肾动脉中,即使在TP受体拮抗剂减少激动剂引起的收缩后,PGI 2也没有引起舒张。事实上,PGI 2(IP)受体没有检测到在血管与蛋白质印迹。此外,我们注意到,在高血压前期阶段开始使用非选择性考克斯抑制剂吲哚美辛治疗,在治疗2个月内,SHR的收缩压升高减弱,心体比降低。这些结果表明,由于缺乏IP受体,PGI 2,这是主要来自考克斯-1介导的代谢,作为一个EDCF在年轻的WKY肾动脉,它增加在高血压前期的条件。此外,我们的数据显示,考克斯抑制开始从高血压前期阶段有降压作用的年轻SHR。
This study aimed to determine whether prostacyclin (PGI2) functions as an endothelium-derived contracting factor (EDCF) in young rat renal arteries, and, if so, we wanted to examine the underlying mechanism(s) and how it changes in prehypertensive conditions. Vessels from Wistar-Kyoto (WKY) and prehypertensive spontaneously hypertensive rats (SHRs) of 25–28 days of age were isolated for functional and biochemical analyses. Result showed that following NO synthase (NOS) inhibition PGI2and the thromboxane-prostanoid (TP) receptor agonist U-46619 evoked contractions in young WKY renal arteries that were similar to those in prehypertensive SHRs. Meanwhile, the endothelial muscarinic receptor agonist ACh evoked an endothelium-dependent contraction under NOS-inhibited conditions and a production of the PGI2metabolite 6-keto-PGF1α; both were sensitive to cyclooxygenase (COX) and/or COX-1 inhibition but higher in prehypertensive SHRs than in young WKYs. Interestingly, in WKY renal arteries PGI2did not evoke relaxation even after TP receptor antagonism that diminished the contraction evoked by the agonist. Indeed, PGI2(IP) receptors were not detected in the vessel with Western blot. Moreover, we noted that treatment with the nonselective COX inhibitor indomethacin, which was started at the prehypertensive stage, blunted the elevation of systolic blood pressure and reduced the heart-to-body ratio in SHR within 2 mo of treatment. These results demonstrate that due to scarcity of IP receptors, PGI2, which is derived mainly from COX-1-mediated metabolism, acts as an EDCF in young WKY renal arteries, and it increases in prehypertensive conditions. Also, our data revealed that COX inhibition starting from the prehypertensive stage has an antihypertensive effect in young SHRs.
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DOI: 10.1161/01.hyp.21.3.280
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