腺苷A1和κ1-阿片受体激动剂对自发性高血压大鼠心脏β-肾上腺素能受体的抑制作用减弱。

Reduced inhibitory actions of adenosine A1 and kappa 1-opioid receptor agonists on beta-adrenoceptors in spontaneously hypertensive rat heart.

Yu X C, Wang H X, Wong T M

Department of Physiology, Faculty of Medicine, University of Hong Kong, Hong Kong.

Clin Exp Pharmacol Physiol. 1997 Dec;24(12):976-7. doi: 10.1111/j.1440-1681.1997.tb02732.x.

Abstract

The modulatory actions of both adenosine A1 and kappa 1-opioid receptor agonists on beta-adrenoceptor stimulation in the heart of both spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were compared. 2. In both types of rats, both R(-)-N6-(2-phenylisopropyl)adenosine (R-PIA), an adenosine A1 receptor agonist, and U50 488H, a kappa 1-opioid receptor agonist, inhibited the stimulatory effects of beta-adrenoceptor activation on electrically induced [Ca2+]i transients measured by a spectrofluorometric method with fura-2/AM as the calcium indicator. The effects of these two agonists were blocked by their respective antagonists, namely 8-cyclopentyl-1,3-diprolxanthine and norbinaltorphimine. 3. The inhibitory actions of both R-PIA and U50 488H on beta-adrenoceptor augmentation of electrically induced [Ca2+]i transients in the heart were more significantly reduced in SHR than in WKY rats, suggesting the negative modulatory actions of endogenous substances on beta-adrenoceptors were impaired in SHR, which may contribute to hypertension.

摘要

比较了腺苷A1受体激动剂和κ1-阿片受体激动剂对自发性高血压大鼠（SHR）和正常血压的Wistar-Kyoto（WKY）大鼠心脏中β-肾上腺素能受体刺激的调节作用。2. 在这两种类型的大鼠中，腺苷A1受体激动剂R(-)-N6-(2-苯异丙基)腺苷（R-PIA）和κ1-阿片受体激动剂U50 488H均抑制了β-肾上腺素能受体激活对以fura-2/AM作为钙指示剂通过荧光分光光度法测量的电诱导[Ca2+]i瞬变的刺激作用。这两种激动剂的作用被它们各自的拮抗剂，即8-环戊基-1,3-二丙基黄嘌呤和去甲丙咪嗪阻断。3. 与WKY大鼠相比，SHR中R-PIA和U50 488H对心脏电诱导[Ca2+]i瞬变的β-肾上腺素能受体增强作用的抑制作用更显著降低，提示内源性物质对β-肾上腺素能受体的负性调节作用在SHR中受损，这可能与高血压的发生有关。