EFFECT OF ADMINISTRATION OF INSULIN ON STREPTOZOTOCIN-INDUCED DIABETIC HYPERTENSION IN RAT

We have reported that streptozotocin-induced insulin-dependent diabetes mellitus in 25% reduced renal mass rats is associated with low-renin, volume-expanded hypertension and that the development of the hypertension can be prevented with insulin. In this study we examined the effect of insulin after the animals had developed sustained hypertension. Normotensive 25% reduced renal mass rats were treated with streptozotocin and, as expected, developed insulin-dependent diabetes mellitus and hypertension. After 4 weeks of sustained hypertension, neutral protamine Hagedorn insulin (6 to 8 IU/d) was administered subcutaneously for 4 weeks. As expected, insulin treatment decreased plasma glucose and increased body weight gain relative to untreated diabetic rats. On the other hand, insulin treatment did not reverse the hypertension and albuminuria. It also did not normalize extracellular fluid volume and plasma renin activity. Furthermore, insulin treatment did not reverse the increase in plasma Na+,K+-ATPase inhibitory activity (determined by both radioimmunoassay and bioassay) and the inhibition of myocardial microsomal Na+,K+-ATPase activity observed in the untreated diabetic hypertensive rats. 5'-Nucleotidase, a membrane marker, was not different between insulin-treated and untreated diabetic rats. These results show that insulin, given as here described, does not reverse the insulin-dependent diabetes mellitus hypertension in 25% reduced renal mass rats once it is established, perhaps because it does not reverse the albuminuria, volume expansion, increase in endogenous digitalis-like substance, and inhibition of cardiovascular muscle cell Na+,K+-ATPase activity.