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

We have reported that streptozotocin-induced insulin-dependent diabete s mellitus in 25% reduced renal mass rats is associated with low-renin , volume-expanded hypertension and that the development of the hyperte nsion can be prevented with insulin. In this study we examined the eff ect of insulin after the animals had developed sustained hypertension. Normotensive 25% reduced renal mass rats were treated with streptozot ocin and, as expected, developed insulin-dependent diabetes mellitus a nd hypertension. After 4 weeks of sustained hypertension, neutral prot amine Hagedorn insulin (6 to 8 IU/d) was administered subcutaneously f or 4 weeks. As expected, insulin treatment decreased plasma glucose an d increased body weight gain relative to untreated diabetic rats. On t he 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 b y 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 differe nt between insulin-treated and untreated diabetic rats. These results show that insulin, given as here described, does not reverse the insul in-dependent diabetes mellitus hypertension in 25% reduced renal mass rats once it is established, perhaps because it does not reverse the a lbuminuria, volume expansion, increase in endogenous digitalis-like su bstance, and inhibition of cardiovascular muscle cell Na+,K+-ATPase ac tivity.