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正常血压和高血压大鼠左心房中的功能性β-肾上腺素能受体

Functional beta-adrenoceptors in the left atrium of normotensive and hypertensive rats.

作者信息

Doggrell S A, Surman A J

机构信息

Department of Pharmacology School of Medicine, University of Auckland, New Zealand.

出版信息

J Auton Pharmacol. 1994 Dec;14(6):425-36. doi: 10.1111/j.1474-8673.1994.tb00623.x.

Abstract
  1. The aim of the study was to characterize the functional beta 1-and beta 2-adrenoceptors of the rat left atrium and to investigate how these functional beta-adrenoceptor responses were altered in hypertension. The contractile responses of the left atrium from Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats to isoprenaline, T-0509 and procaterol were characterized. Subsequently, the effects of selective beta 1-(bisoprolol) and beta 2 (ICI 118,551)-adrenoceptor antagonists were investigated on these responses. 2. The maximal combined contractile responses of the rat left atrium to cardiac stimulation and CaCl2, isoprenaline, T-0509 or procaterol were not altered by hypertension. 3. The sensitivities to CaCl2 (pD2 on WKY left atrium = 2.99), isoprenaline (8.82) and T-0509 (8.84) were not altered by hypertension. There was an increase in sensitivity to procaterol from a pD2 value of 7.21 to 7.61 in the left atrium of the SH rat. 4. The basal tension induced by cardiac stimulation alone was inhibited by bisoprolol at > or = 10(-8) M and by ICI 118,551 at > or = 10(-7) M and this inhibitory effect is probably due to membrane stabilizing activity. 5. The pKB values for bisoprolol against isoprenaline, T-0509 and procaterol on the WKY were 8.43, 8.68 and 8.18, respectively, and were not different from SH rat left atrium. 6. The pKB value for ICI 118,551 against isoprenaline was increased from 7.06 on the WKY to 7.44 on the SH rat left atrium. The pKB values for ICI 118,551 against T-0509 and procaterol on the WKY were 7.18 and 8.14, respectively and were not significantly different from the SH rat left atrium values. 7. These results suggest that: (a) procaterol stimulates the beta 1-, in addition to, the beta 2-adrenoceptors of the rat left atrium; (b) functional beta 1-adrenoceptors are not altered in hypertension, and (c) there is probably an increase in the affinity of procaterol and isoprenaline for the beta 2-adrenoceptors which underlies the small increase in the functional beta 2-adrenoceptor response in hypertension.
摘要
  1. 本研究的目的是对大鼠左心房的功能性β1和β2肾上腺素能受体进行表征,并研究在高血压状态下这些功能性β肾上腺素能受体反应是如何改变的。对Wistar-Kyoto(WKY)大鼠和自发性高血压(SH)大鼠左心房对异丙肾上腺素、T-0509和丙卡特罗的收缩反应进行了表征。随后,研究了选择性β1-(比索洛尔)和β2(ICI 118,551)肾上腺素能受体拮抗剂对这些反应的影响。2. 高血压并未改变大鼠左心房对心脏刺激、氯化钙、异丙肾上腺素、T-0509或丙卡特罗的最大联合收缩反应。3. 高血压并未改变对氯化钙(WKY左心房的pD2 = 2.99)、异丙肾上腺素(8.82)和T-0509(8.84)的敏感性。SH大鼠左心房对丙卡特罗的敏感性从pD2值7.21增加到7.61。4. 单独心脏刺激诱导的基础张力在比索洛尔浓度≥10^(-8) M时受到抑制,在ICI 118,551浓度≥10^(-7) M时受到抑制,这种抑制作用可能归因于膜稳定活性。5. 比索洛尔对WKY大鼠左心房的异丙肾上腺素、T-0509和丙卡特罗的pKB值分别为8.43、8.68和8.18,与SH大鼠左心房无差异。6. ICI 118,551对异丙肾上腺素的pKB值从WKY大鼠左心房的7.06增加到SH大鼠左心房的7.44。ICI 118,551对WKY大鼠左心房的T-0509和丙卡特罗的pKB值分别为7.18和8.14,与SH大鼠左心房的值无显著差异。7. 这些结果表明:(a)丙卡特罗除了刺激大鼠左心房的β2肾上腺素能受体外,还刺激β1肾上腺素能受体;(b)功能性β1肾上腺素能受体在高血压中未改变;(c)丙卡特罗和异丙肾上腺素对β2肾上腺素能受体的亲和力可能增加,这是高血压中功能性β2肾上腺素能受体反应略有增加的基础。

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