Reduced responsiveness of [Ca2+]i to adenosine A1- and A2-receptor stimulation in the isoproterenol-stimulated ventricular myocytes of spontaneously hypertensive rats
Abstract
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 agoni...Continue Reading
References
Differential antiarrhythmic potency of adenosine in normotensive and spontaneously hypertensive rats
Pharmacological characterization of A2-adenosine receptors in guinea-pig ventricular cardiomyocytes.
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