Abstract
1. The contractile function of diabetic hearts is impaired. In addition, the responsiveness of diabetic cardiac muscle to sympathetic stimulation is altered. Previous studies have revealed a depressed response to beta-adrenoceptor stimulation; however, the response to alpha-adrenoceptor activation remains controversial. Because alpha- and beta-adrenoceptor agonists increase cardiac contractility, largely through increased mobilization of intracellular Ca2+, the aim of the present study was to investigate the effects of alpha- and beta-adrenoceptor stimulation on intracellular Ca2+ handling in cardiac myocytes from streptozotocin-induced diabetic rats. 2. Intracellular Ca2+ was measured using fura-2. Under basal conditions (27 degrees C, 2.5 mmol/L extracellular [Ca2+], 0.3 Hz stimulation), there was no significant difference in resting or peak Ca2+ levels between control and diabetic cardiomyocytes. However, the time course of the intracellular Ca2+ transient was significantly prolonged in cells from diabetic hearts. 3. The beta-adrenoceptor agonist orciprenaline (at 10(-7) and 10(-6) mol/L) increased the amplitude of the Ca2+ transient in both groups; however, the extent of potentiation was less in diabetic compared with control cardiomyocytes. Orciprenaline decreased the duration of the transient to the same extent in both groups. 4. The alpha-adrenoceptor agonist phenylephrine (at 10(-7) and 10(-6) mol/L) had no effect on the Ca2+ transient in control myocytes but caused a significant concentration-dependent increase in its amplitude in diabetic cardiomyocytes. Phenylephrine had no effect on the time course of the transient in either group. 5. These results demonstrate differential effects of insulin-dependent diabetes on the responsiveness of cardiomyocytes to alpha- and beta-adrenoceptor stimulation. The heightened response to alpha-adrenoceptor stimulation observed in diabetic cardiomyocytes may partly compensate for the diminished myocardial beta-adrenoceptor response.
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