SUSCEPTIBILITY OF SPONTANEOUSLY HYPERTENSIVE RATS TO THE DIABETOGENICEFFECTS OF STREPTOZOTOCIN

Several studies have utilized the spontaneously hypertensive (SHR) dia betic rat to document the synergistic deleterious consequences of diab etes and hypertension on various organ systems. However, whether these effects are due entirely to the overlapping pathological states or pa rtially result from a greater susceptibility of SHR rats to the diabet ogenic effects of streptozotocin (STZ) is unclear. The present study w as conducted to examine if strain-dependent variabilities in the STZ-i nduced diabetic state could also contribute to the pronounced complica tions previously observed in the SHR diabetic rat. To eliminate a poss ible modulating influence of severe hypertension on the beta-cytotoxic efficacy of STZ, SHR (SHRD), and Wistar (WisD) rats were injected wit h STZ (55 mg/kg i.v.) at 7-8 weeks of age, a time when there was no si gnificant difference in systolic blood pressure between both strains. An oral glucose tolerance test was performed at 1 week following STZ a nd animals were killed at 2 weeks. Although both diabetic groups were equally hyperglycemic in the fed state, only SHRD rats had significant ly elevated fasted glycemia at 1 week. Plasma insulin levels in the fe d state or in response to oral glucose, as well as pancreatic insulin contents were diminished to a greater extent in the SHRD group relativ e to WisD. Fed plasma triglyceride (TG) levels were elevated only in t he SHRD group, in association with a 4-fold reduction in basal circula ting lipoprotein lipase (LPL) activity. However, plasma TG clearance a nd LPL activity in response to i.v. heparin were not significantly alt ered in SHRD relative to SHR controls. The results in this study indic ate that when evaluating the combined effects of diabetes and spontane ous hypertension, the STZ dose should be titrated to obtain an identic al degree of diabetes in the SHR and a normotensive strain. In this re gard, 45 (SHR) and 55 (Wistar) mg/kg STZ produced an identical milieu of diabetes.