ANP infusion increased hematocrit and decreased plasma volume (PV) by inducing a shift of plasma fluid from the vascular towards the interstitial compartment. Rats with experimental diabetes mellitus resulting from streptozotocin (STZ) treatment exhibit renal resistance to infused ANP. To determine if resistance to the extrarenal actions of ANP also occurs in these conditions, changes in arterial pressure and hematocrit were measured during infusion of ANP (I mug/kg/min for 45 min) in anesthetized binephrectomized rats 2-3 weeks after induction of diabetes. Blood glucose was significantly elevated in diabetic when compared to control and insulin-treated diabetic rats. Arterial pressure decreased similarly in control, diabetic and insulin-treated diabetic rats (by 7.6 +/- 1.6, 9.6 +/- 1.9 and 8.2 +/- 2 % respectively; all p < 0.002). In control rats, hematocrit increased progressively to a maximal value of 9.5 +/- 0.9 % corresponding to a decrease in PV of 16 +/- 1 %. In contrast, the ANP-induced increase in hematocrit was markedly blunted in diabetic rats (1.6 +/- 0.8 %; p < 0.0001 vs ANP infusion in control rats), corresponding to a decrease in PV of only 2.2 +/- 1 %. In addition, reducing the hyperglycemia in diabetic rats by insulin therapy restored the increase in hematocrit to ANP (8.5 +/- 1.1 %; p < 0.0001 and p = NS vs ANP infusion in diabetic and control rats respectively). PV, measured at the end of the infusion period, did not differ between contol and insulin-treated diabetic rats infused with ANP (21.3 +/- 1.4 and 22.5 +/- 1.4 ml/kg). In contrast, PV was significantly higher in diabetes (32 +/- 1.1 ml/kg) as compared to both ANP or vehicle (25.2 +/- 1.1 ml/kg) infused control rats. This study demonstrate that a) the effect of ANP on hematocrit and volemia is blunted in STZ-induced diabetes while it's hypotensive action is preserved, and b) restoring the glucose levels to normal in diabetic rats by insulin treatment normalizes the hemoconcentrating effect to exogenous administered ANT. Such an effect may account for the plasma volume expansion observed in untreated diabetic rats.
