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

Abstract

1. 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.