Reduced inhibitory actions of adenosine A1 and kappa 1-opioid receptor agonists on beta-adrenoceptors in spontaneously hypertensive rat heart.
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.
Yu
X C
XC
Department of Physiology, Faculty of Medicine, University of Hong Kong, Hong Kong.
Wang
H X
HX
Wong
T M
TM
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D005456:Fluorescent Dyes; D016257:Fura-2; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006973:Hypertension / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D009638:Norepinephrine / Q000494:pharmacology; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D013053:Spectrophotometry
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D005456:Fluorescent Dyes; D058906:Purinergic P1 Receptor Agonists; D017473:Receptors, Opioid, kappa; D010660:Phenylisopropyladenosine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D007545:Isoproterenol; D002118:Calcium; D016257:Fura-2; D009638:Norepinephrine