Effects of single high-dose and multiple low-dose streptozotocin on contraction and intracellular Ca2+ in ventricular myocytes from diabetes resistant and susceptible rats

Abstract

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.