Reduced responsiveness of [Ca2+]i to adenosine A1- and A2-receptor stimulation in the isoproterenol-stimulated ventricular myocytes of spontaneously hypertensive rats.
To determine the modulatory action of adenosine-receptor stimulation on [Ca2+]i responses to beta-adrenoceptor stimulation in the heart of the spontaneously hypertensive rat (SHR), the electrically induced [Ca2+]i transient in response to isoproterenol (ISO) in single ventricular myocytes pretreated with adenosine agonists in SHRs and its normotensive control Wistar-Kyoto (WKY) rats was measured with a spectrofluorometric method by using fura-2/AM as the calcium indicator. In both types of rat, ISO at 0.001-1 microM augmented the electrically induced [Ca2+]i transient, and the effect was blocked by a beta-adrenoceptor blocker, propranolol. In SHRs that did not exhibit cardiac hypertrophy, the resting level of [Ca2+]i and the amplitude of the electrically induced [Ca2+]i transient were the same as those in WKY rats, whereas the augmentation of the electrically induced [Ca2+]i transient in response to ISO was significantly lower than that in WKY rats. In WKY rats, the effects of ISO on the electrically induced [Ca2+]i transient were inhibited by the adenosine A1-receptor agonist, R(-)-N6-(2-phenylisopropyl)adenosine (R-PIA) at 0.01-10 microM. In contrast, the effects of ISO were further enhanced by the adenosine A2-receptor agonist, N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl)]adenosine (DPMA) at 1-10 microM. In SHRs, the inhibitory effect of R-PIA was significantly reduced, whereas the excitatory effect of DPMA was absent. The effects of both adenosine-receptor agonists in both types of rat were abolished by the respective adenosine-receptor antagonists, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and 3,7-dimethyl-1-propargylxanthine (DMPX). The results indicate that the modulatory actions of adenosine-receptor stimulation on [Ca2+]i response to beta-adrenoceptor stimulation in the hearts of SHRs are reduced, which is independent of cardiac hypertrophy.
Tang
X L
XL
Department of Physiology, Institute of Cardiovascular Science and Medicine, The University of Hong Kong, Hong Kong.
Wang
H X
HX
Cho
C H
CH
Wong
T M
TM
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004558:Electric Stimulation; D006352:Heart Ventricles / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D002316:Cardiotonic Agents; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D014665:Vasodilator Agents; D014970:Xanthines; C056426:CGS 24012; C047235:N-(1-methyl-2-phenylethyl)adenosine; C057837:3,7-dimethyl-1-propargylxanthine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D007545:Isoproterenol; D013805:Theobromine; D002118:Calcium