Contractile responses of aortae from WKY and SHR to vasoconstrictors
Contractile responses of aortae from WKY and SHR to vasoconstrictors
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DOI：
10.1081/ceh-200031826
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发表时间：
2004-08-01
影响因子：
12.3
通讯作者：
Regoli, D
中科院分区：
文献类型：
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作者：
Gendron, G;Gobeil, F;Regoli, D
取4、8、16周龄自发性高血压大鼠(SHR)和京都Wistar大鼠(WKY)的主动脉制成环，用于测定5种血管收缩药的作用。取内皮，选择性测定氯化钾(KCl)、苯肾上腺素(Phe)、血管紧张素-II(Ang II)、内皮素-1(ET-1)和人尾加压素-II(U-II)引起的收缩反应。这些反应被认为来自于特定受体(即α(1)、AT(1)、ETA和UT-II)的激活或来自KCl对平滑肌纤维的去极化。用不同浓度的拮抗剂哌唑嗪、氯沙坦、BQ-123和[Orn(8)]-UII对这些受体系统进行药理学研究。这项研究的主要目的是探索可能干预自发性高血压患者高血压发生和维持的机制或因素。结果表明，SHR和WKY的离体主动脉含有收缩部位(受体)，其药理特征(激动剂为PEC(50)，拮抗剂为Pa(2))与其他生物系统非常相似，应被认为是Alpha(1)、AT(1)、Eta和UT-II受体类型的典型。与同龄WKY相比，SHR 4(非高血压)、8周龄和16周龄(高血压)的Aortae对缩血管药的最大收缩反应减弱。用五种血管收缩药观察到的主动脉的这些意想不到的降低反应，可能归因于非特异性病变。KCl、Phe和U-II组SHR的主动脉最大收缩从4周增加到16周，Ang II组降低，ET-1组保持稳定。U-II诱导的WKY最大收缩也呈年龄依赖性增加。提示自发性高血压大鼠的主动脉在体外经历了早期的重塑，导致收缩能力降低，在体内可能导致血管僵硬。这一过程中涉及的因子似乎源于遗传，因为它们在高血压之前就存在：它们可能有助于改变高血压动物的主动脉顺应性，甚至可能改变血管阻力，因此是高血压的原因而不是结果。
Aortae taken from spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats aged 4, 8 and 16 weeks were prepared as rings and used to measure the effects of five vasoconstrictors. The endothelium was removed in order to measure selectively the contractile responses induced by potassium chloride (KCl), phenylephrine (PHE), angiotensin-II (Ang II), endothelin-1 (ET-1) and human urotensin-II (U-II). These responses were assumed to derive from the activation of specific receptors (namely alpha(1), AT(1), ETA and UT-II) or from depolarization of the smooth muscle fibers by KCl. Specific antagonists prazosin, losartan, BQ-123 and [Orn(8)]-UII were used at various concentrations for a pharmacological characterization of these latter receptor systems. The primary purpose of the study was to explore mechanisms or factors that may intervene in the development and maintenance of high blood pressure in SHR. Results indicate that isolated aortae of SHR and WKY contain contractile sites (receptors) whose pharmacological profiles (pEC(50) for agonists, pA(2) for antagonists) are very similar to those of other biological systems and should be considered as typical for the alpha(1), AT(1), ETA and UT-II receptor types. Aortae taken from SHR 4 (non hypertensive), 8 and 16 weeks old (hypertensive) responded to the vasoconstrictors with reduced maximal contractions compared to those of age-matched WKY. These unexpected reduced responses of aortae, observed with the five vasoconstrictors, may be attributed to a non specific lesions. Maximal contraction of aortae from SHR increased from 4 to 16 weeks for KCl, PHE and U-II, decreased for Ang II, and remained stable for ET-1. There was also an age-dependent increase of maximal contraction induced by U-II in WKY. It is suggested that aortae from SHR undergo early remodelling that leads to reduced contractility in vitro and possibly to vessel rigidity in vivo. The factors involved in this process appear to be of genetic origin since they are present before hypertension: they may contribute to modify aortic compliance and perhaps vascular resistance in hypertensive animals and thus being the cause and not the consequence of high blood pressure.