Tempol selectively attenuates angiotensin II evoked vasoconstrictor responses in spontaneously hypertensive rats
Tempol selectively attenuates angiotensin II evoked vasoconstrictor responses in spontaneously hypertensive rats
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Tempol 选择性减弱血管紧张素 II 在自发性高血压大鼠中引起的血管收缩反应
DOI：
10.1097/00004872-200207000-00025
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发表时间：
2002
影响因子：
4.9
通讯作者：
H. Di Wang
中科院分区：
文献类型：
--
作者：
S. Shastri;V. Gopalakrishnan;R. Poduri;H. Di Wang
目的探讨超氧阴离子是否介导自发性高血压大鼠(SHR)血管对激动剂的收缩反应。方法观察超氧化物歧化酶模拟物4-羟基-2，2，6，6-四甲基哌啶氧基(Tempol)对血管紧张素II(Ang II)、内皮素-1(ET-1)、苯肾上腺素和氯化钾的影响。观察坦普尔对血管紧张素Ⅱ诱导的主动脉环超氧化物生成的影响。结果SHR的主动脉环对激动剂的最大张力(Emax)无明显差异，但血管紧张素Ⅱ最大反应(EC50)的50%所需浓度的负对数较低(P<0.05)。在SHR的MVBS中，对Ang II、ET-1和苯肾上腺素的反应所获得的Emax值较大，但EC50值不大。在血管内皮细胞完整的主动脉和MVB制剂中，坦泊尔显著且选择性地降低血管紧张素转换酶II的Emax。血管紧张素Ⅱ引起的Emax降低在SHR(P<；0.01)比WKY大鼠(P<；0.05)或SD大鼠(P<；0.05)更明显。当加入一氧化氮合酶抑制剂或内皮被剥离时，坦普尔的抑制作用消失。当缓冲液中加入temol时，Ang II在完整和去内皮的SHR的主动脉环上引起的荧光素化学发光的显著增加被取消。结论超氧阴离子浓度增加可能通过猝灭血管舒张剂一氧化氮而介导血管紧张剂对血管紧张素Ⅱ的收缩反应，但对其他激动剂的收缩反应无此作用。这可能是自发性高血压大鼠血管收缩反应过度的原因。
Objective To assess whether superoxide anions mediate vasoconstrictor responses to agonists in blood vessels of spontaneously hypertensive rats (SHRs). Methods The effect of the superoxide dismutase mimetic, 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (tempol), on responses to angiotensin II (Ang II), endothelin-1, phenylephrine and potassium chloride was determined in aortic rings and perfused mesenteric vascular beds (MVB) of adult male rats of the Sprague–Dawley, Wistar–Kyoto (WKY) and spontaneously hypertensive (SHR) strains. The effect of tempol on Ang II-evoked superoxide production was assessed in aortic rings. Results There were no differences in the maximum tension (Emax) attained in response to agonists, but the negative logarithm of the concentration required to produce 50% of the maximal response (EC50) for Ang II was lower (P < 0.05) in aortic rings of SHRs. In the MVBs of SHRs, the Emax but not the EC50 values attained in response to Ang II, endothelin-1 and phenylephrine were greater. Tempol significantly and selectively reduced the Emax of Ang II in both aorta and MVB preparations with intact endothelium. The reduction in Emax attained in response to Ang II was more pronounced in SHRs (P < 0.01) than in WKY rats (P < 0.05) or Sprague–Dawley rats (P < 0.05). The inhibitory effect of tempol was absent when a nitric oxide synthase inhibitor was included or endothelium was denuded. A significant increase in lucigenin chemiluminescence evoked by Ang II in both intact and endothelium-denuded aortic rings of SHRs was abolished when tempol was included in the buffer. Conclusions These data suggest that increased superoxide anions mediate vasoconstrictor responses to Ang II, but not to other agonists, in an endothelium-dependent manner, by quenching vasodilatory mediator, nitric oxide. This may account for the exaggerated vasoconstrictor responses to Ang II in SHRs.
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影响因子：
8.3
作者：
Romero, JC;Reckelhoff, JF
通讯作者：
Reckelhoff, JF
影响因子：
15.9
作者：
Rajagopalan, S;Kurz, S;Harrison, DG
通讯作者：
Harrison, DG
影响因子：
20.1
作者：
GRIENDLING, KK;MINIERI, CA;ALEXANDER, RW
通讯作者：
ALEXANDER, RW
影响因子：
20.1
作者：
Fukui, T;Ishizaka, N;Griendling, KK
通讯作者：
Griendling, KK
影响因子：
37.8
作者：
Laursen, JB;Rajagopalan, S;Harrison, DG
通讯作者：
Harrison, DG