Effects of Isoprenaline on ventricular myocyte shortening and Ca²⁺ transport in the Zucker rat

Obesity is an important risk factor for diabetes mellitus (DM) which is a major global health problem. Electro-mechanical dysfunction has been extensively described in diabetic heart and cardiovascular complications are an important cause of mortality and morbidity in diabetic patients. Objectives: To examine the effects of Isoprenaline (ISO) in obesity and diabesity on ventricular myocyte shortening and Ca²⁺ transport in Zucker fatty (ZF), Zucker diabetic fatty (ZDF) in comparison to Zucker lean (ZL) rats. Methods: Myocyte shortening and intracellular Ca²⁺ were investigated with video imaging and fluorescence photometry, respectively. Results: The amplitude of Isoprenaline stimulated shortening was significantly (p < 0.05) decreased in ZDF and ZF compared to ZL myocytes. The amplitude of Isoprenaline stimulated Ca²⁺ transient was also significantly (p < 0.05) reduced in ZF compared to ZL and modestly reduced in ZDF compared to ZL myocytes. Mean Isoprenaline stimulated time to peak along with time to half relaxation of shortening were unchanged in ZDF and ZF compared to ZL myocytes. Mean Isoprenaline stimulated time to peak Ca²⁺ transient was significantly shortened in ZF compared to ZL myocytes. Time to half decay of the Ca²⁺ transient was considerably prolonged in ZDF compared to ZL myocytes. Amplitude of Isoprenaline stimulated caffeine-evoked Ca²⁺ transients were significantly reduced in ZDF and ZF in comparison to ZL myocytes. Conclusion: Isoprenaline was less effective at generating an increase in the amplitude of shortening in ZDF and ZF in comparison to ZL myocytes and defects in Ca²⁺ signaling, and in particular SR Ca²⁺ transport, might partly underlie these abnormalities.