Effects of hyperosmotic shrinking on ventricular myocyte shortening and intracellular Ca(2+) in streptozotocin-induced diabetic rats.
Evidence exists for a specific diabetic cardiomyopathy independent of concurrent vascular disease. We tested the hypothesis that chronic hyperglycaemia found in streptozotocin- (STZ) induced diabetic rats leads to an altered response to and contractile effects of hyperosmotic shrinkage in ventricular myocytes. Analysis confirmed significant hyperglycaemia and revealed significant blood hyperosmolarity in STZ-treated rats. Myocyte volume changes, shortening and intracellular Ca(2+) ([Ca(2+)](i)) transients were measured in cells superfused with normal Tyrode (NT, 300 mmol/kg) and then hyperosmotic Tyrode (HT, 440 mmol/kg) at 35-36 degrees C. Shrinking significantly reduced the amplitude of shortening, whilst the [Ca(2+)](i) transient was significantly increased. The time course of both shortening and the [Ca(2+)](i) transient were prolonged in myocytes from STZ-treated compared to control rats. Time to peak shortening was 130.3 ms in STZ compared to 100.2 ms in control myocytes. Time to peak [Ca(2+)](i) transient was 70.8 ms in STZ compared to 44.6 ms in control myocytes and the time from peak to half recovery was 191.0 ms in STZ compared to 169.1 ms in control myocytes. Fractional SR Ca(2+) release, assessed by the application of caffeine, was increased by shrinking. However, the effects of raised extracellular osmolarity on volume changes, contractility and [Ca(2+)](i) were not altered by the chronic hyperglycaemia found in STZ-treated rats.
Howarth
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Department of Physiology, Faculty of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, United Arab Emirates. chris.howarth@uaeu.ac.ae
Qureshi
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MA
White
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D000818:Animals; D002118:Calcium / Q000378:metabolism*; D048429:Cell Size / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D006982:Hypertonic Solutions / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D009994:Osmolar Concentration; D009997:Osmotic Pressure; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D006982:Hypertonic Solutions; D002118:Calcium