34 Rats with streptozotocin diabetes mellitus are resistant to the action of atrial natriuretic peptide to increase vascular permeability

Abstract

Introduction: Atrial natriuretic peptide (ANP) infusion increases hematocrit and decreases plasma volume by inducing a shift of plasma fluid from the vascular towards the interstitial compartment. Rats with experimental diabetes mellitus resulting from streptozotocin treatment exhibit renal resistance to infused ANP. Methods: To determine whether resistance to the extrarenal actions of ANP also occurs under these conditions, changes in arterial pressure and hematocrit were measured during infusion of ANP (1 μg/kg per min for 45 min) in anesthetized binephrectomized rats 2–3 weeks after induction of diabetes. Results: Blood glucose was significantly elevated in diabetic compared with control and insulin-treated diabetic rats. Arterial pressure decreased similarly in control, diabetic and insulin-treated diabetic rats (by 7.611.6, 9.611.9 and 8.212%, respectively; all P<0.002). In control rats, hematocrit increased progressively to a maximal value of 9.510.9% corresponding to a decrease in plasma volume of 1611%. In contrast, the ANP-induced increase in hematocrit was markedly blunted in diabetic rats (1.610.8%, P<0.0001 versus ANP infusion in control rats), corresponding to a decrease in plasma volume of only 2.211%. In addition, reducing the hyperglycemia in diabetic rats by insulin therapy restored the increase in hematocrit to ANP (8.511.1%, P<0.0001 and P=NS versus ANP infusion in diabetic and control rats respectively). Plasma volume measured at the end of the infusion period was similar in control and insulin-treated diabetic rats infused with ANP (21.311.4 and 22.511.4 ml/kg). In contrast, plasma volume was significantly higher in diabetes (3211.1 ml/kg) compared with both ANP and vehicle (25.211.1 ml/kg) infused control rats. Conclusions: This study demonstrates that (1) the effect of ANP on hematocrit and volemia is blunted in streptozotocin-induced diabetes while its hypotensive action is preserved, and (2) restoring the glucose levels to normal in diabetic rats by insulin treatment normalizes the hemoconcentrating effect to exogenous administered ANP. Such an effect may account for the plasma volume expansion observed in untreated diabetic rats.