Alterations in vasoconstrictor responses to the endothelium-derived contracting factor uridine adenosine tetraphosphate are region specific in DOCA-salt hypertensive rats.

Alterations in vasoconstrictor responses to the endothelium-derived contracting factor uridine adenosine tetraphosphate are region specific in DOCA-salt hypertensive rats.
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DOI:
10.1016/j.phrs.2011.09.005
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发表时间:
2012-01
影响因子:
9.3
通讯作者:
Webb, R. Clinton
Webb, R. Clinton
中科院分区:
医学1区
文献类型:
--
作者:
Matsumoto, Takayuki;Tostes, Rita C.;Webb, R. Clinton

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尿苷腺苷四磷酸(Up 4A)是一种新的内皮源性收缩因子,含有嘌呤和嘧啶两个部分,可激活嘌呤能P2 X和P2 Y受体。本研究旨在比较去氧皮质酮醋酸盐(DOCA盐)和对照大鼠不同血管区域[胸主动脉、基底动脉、肠系膜小动脉和股动脉]对Up 4A和其他核苷酸如ATP(P2 X/P2 Y激动剂)、UTP(P2 Y2/P2 Y 4激动剂)、UDP(P2 Y 6激动剂)和α,β-亚甲基ATP(P2 X1激动剂)的收缩反应。DOCA-盐组大鼠与对照单侧肾切除(Uni)大鼠比较:(1)胸主动脉Up 4A、ATP和UTP诱导的收缩无变化,(2)基底动脉Up 4A、ATP、UTP和UDP诱导的收缩增加,P2 X1表达减少,而P2 Y2和P2 Y 6表达无变化;(3)在肠系膜小动脉,Up 4A引起的收缩减弱,UDP引起的收缩增强,P2 Y2和P2 X1表达减弱,P2 Y 6表达增强;(4)股动脉Up 4A、UTP和UDP诱导的收缩反应增强,而P2 Y2、P2 Y 6和P2 X1的表达无明显变化。α,β-亚甲基ATP诱导的收缩呈钟形,与DOCA盐大鼠相比,Uni大鼠基底动脉和肠系膜动脉在较低浓度下达到最大收缩。这些结果表明,Up 4A诱导的收缩是异质性的影响,在不同的血管床在动脉高压。P2 Y受体激活可能有助于增强Up 4A诱导的基底动脉和股动脉收缩。血管对Up 4A的反应性的这些变化可能适应于高血压引起的血管改变。
Uridine adenosine tetraphosphate (Up4A) has been recently identified as a novel and potent endothelium-derived contracting factor and contains both purine and pyrimidine moieties, which activate purinergic P2X and P2Y receptors. The present study was designed to compare contractile responses to Up4A and other nucleotides such as ATP (P2X/P2Y agonist), UTP (P2Y2/P2Y4 agonist), UDP (P2Y6 agonist), and α,β-methylene ATP (P2X1 agonist) in different vascular regions [thoracic aorta, basilar, small mesenteric, and femoral arteries] from deoxycorticosterone acetate-salt (DOCA-salt) and control rats. In DOCA-salt rats [vs. control uninephrectomized (Uni) rats]: (1) in thoracic aorta, Up4A-, ATP-, and UTP-induced contractions were unchanged; (2) in basilar artery, Up4A-, ATP-, UTP- and UDP-induced contractions were increased, and expression for P2X1, but not P2Y2 or P2Y6 was decreased; (3) in small mesenteric artery, Up4A-induced contraction was decreased and UDP-induced contraction was increased; expression of P2Y2 and P2X1 was decreased whereas P2Y6 expression was increased; (4) in femoral artery, Up4A-, UTP-, and UDP-induced contractions were increased, but expression of P2Y2, P2Y6 and P2X1 was unchanged. The α,β-methylene ATP-induced contraction was bell-shaped and the maximal contraction was reached at a lower concentration in basilar and mesenteric arteries from Uni rats, compared to arteries from DOCA-salt rats. These results suggest that Up4A-induced contraction is heterogenously affected among various vascular beds in arterial hypertension. P2Y receptor activation may contribute to enhancement of Up4A-induced contraction in basilar and femoral arteries. These changes in vascular reactivity to Up4A may be adaptive to the vascular alterations produced by hypertension.
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