Effects of single high-dose and multiple low-dose streptozotocin on contraction and intracellular Ca2+ in ventricular myocytes from diabetes resistant and susceptible rats.
Administration of a single high-dose (SHD) of streptozotocin (STZ) to young adult rats causes a diabetic cardiomyopathy. Albino Oxford (AO) and Dark Agouti (DA) inbred strains of rats are susceptible to developing diabetes when administered a SHD of STZ but differ in susceptibility to multiple low-dose (MLD) STZ. We have investigated the effects of SHD and MLD-STZ on contraction and intracellular Ca2+, measured with fura-2, in ventricular myocytes from AO and DA rats at 18-20 weeks after treatment. Time to peak shortening was significantly prolonged in myocytes from DA rats after SHD-STZ but was not altered in DA rats after MLD-STZ or in AO rats by either MLD or SHZ-STZ treatment. Time to peak shortening in myocytes from DA control and DA rats after SHD-STZ were 88+/-2 ms and 107+/-4 ms, respectively. Time to half relaxation and the amplitude of myocyte shortening were not altered in AO or DA rats by either MLD or SHD-STZ treatment. Amplitude, time to peak fura-2 transient and time to half relaxation of the fura-2 transient were not significantly altered in AO or DA rats by either MLD or SHD-STZ treatment. Contractile defects reported in myocytes from SHD-STZ treated DA rats may be a consequence of altered myofilament sensitivity to Ca2+. The hyperglycaemic effects of MLD-STZ and SHD-STZ induced diabetes was much greater in DA compared to AO rats and the effects of the hyperglycaemia on the time-course of ventricular myocyte contraction was most profound in DA rats after SHD-STZ.
Howarth
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FC
Department of Physiology, Faculty of Medicine & Health Sciences, United Arab Emirates University, Al Ain, UAE. chris.howarth@uaeu.ac.ae
Qureshi
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A
Shahin
A
A
Lukic
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ML
D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin / Q000008:administration & dosage / Q000494:pharmacology*
D013311:Streptozocin; D002118:Calcium