内皮在高血压大鼠腺苷受体介导的血管舒张中的作用。
Role of endothelium in adenosine receptor-mediated vasorelaxation in hypertensive rats.
作者信息
Fahim M, Hussain T, Mustafa S J
机构信息
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858, USA.
出版信息
Fundam Clin Pharmacol. 2001 Oct;15(5):325-34. doi: 10.1046/j.1472-8206.2001.00042.x.
The present study was designed to investigate the role of endothelium derived relaxing factor nitric oxide (NO) in adenosine A2 receptor mediated vasorelaxation in normotensive (WKY) and hypertensive (SHR) rat aortic ring preparations. Adenosine analogues, 2-chloroadenosine (CAD) and 5-ethylcarboxamidoadenosine (NECA) produced concentration-dependent (10(-9)-10(-4) M) relaxation in phenylephrine (1 x 10(-6) M) precontracted vascular rings, which was significantly shifted to the right in SHR compared to WKY rats. Endothelium removal attenuated CAD and NECA relaxation responses in both SHR and WKY and abolished the difference in relaxation between SHR and WKY vascular tissues. The relaxation response to CAD was antagonised by adenosine A2 receptor antagonist, 8-sulfophenyltheophylline (8-SPT, 50 x 10(-6) M). The antagonism by 8-SPT was lower in SHR as compared to WKY tissues. L-monomethylarginine (L-LMMA) (30 x 10(-6) M) significantly shifted the CAD relaxation to the right, which was reversed by the addition of L-arginine (100 x 10(-6) M) in both SHR and WKY rats. However, the rightward shift by L-NMMA was smaller in SHR compared to WKY vascular tissues. Vasorelaxation response to acetylcholine (1 x 10(-6) M) was significantly inhibited (50%) in SHR rings compared to WKY. The relaxation produced by sodium nitroprusside (10(-9)-10(-5) M) in endothelium-intact and -denuded aortic rings showed no difference between SHR and WKY. Isoproterenol produced concentration-dependent (10-9-10-5 M) relaxation, which was shifted to the right in SHR compared to WKY rings with an intact endothelium, while the removal of endothelium abolished the difference in the response between SHR and WKY. The results suggest: (i) adenosine A2 receptors mediate vasorelaxation in part through endothelium possibly by releasing nitric oxide (NO); (ii) the impairment of endothelium may be one of the factors for the attenuation of adenosine receptor and receptor-mediated responses in SHR.
本研究旨在探讨内皮源性舒张因子一氧化氮（NO）在正常血压（WKY）和高血压（SHR）大鼠主动脉环标本中腺苷A2受体介导的血管舒张中的作用。腺苷类似物2-氯腺苷（CAD）和5-乙基羧酰胺腺苷（NECA）在去氧肾上腺素（1×10⁻⁶ M）预收缩的血管环中产生浓度依赖性（10⁻⁹ - 10⁻⁴ M）舒张，与WKY大鼠相比，SHR中的这种舒张明显右移。去除内皮减弱了SHR和WKY中CAD和NECA的舒张反应，并消除了SHR和WKY血管组织之间舒张的差异。对CAD的舒张反应被腺苷A2受体拮抗剂8-磺苯基茶碱（8-SPT，50×10⁻⁶ M）拮抗。与WKY组织相比，8-SPT在SHR中的拮抗作用较低。L-单甲基精氨酸（L-LMMA）（30×10⁻⁶ M）使CAD舒张明显右移，在SHR和WKY大鼠中加入L-精氨酸（100×10⁻⁶ M）可逆转这种右移。然而，与WKY血管组织相比，L-NMMA在SHR中引起的右移较小。与WKY相比，SHR环中对乙酰胆碱（1×10⁻⁶ M）的血管舒张反应明显受到抑制（50%）。硝普钠（10⁻⁹ - 10⁻⁵ M）在有内皮和无内皮的主动脉环中产生的舒张在SHR和WKY之间没有差异。异丙肾上腺素产生浓度依赖性（10⁻⁹ - 10⁻⁵ M）舒张，与有完整内皮的WKY环相比，SHR中的这种舒张右移，而去除内皮消除了SHR和WKY之间反应的差异。结果表明：（i）腺苷A2受体部分通过内皮介导血管舒张，可能是通过释放一氧化氮（NO）；（ii）内皮功能受损可能是SHR中腺苷受体及受体介导反应减弱的因素之一。
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