BLUNTED EFFECT OF ANP ON HEMATOCRIT AND PLASMA-VOLUME IN STREPTOZOTOCIN-INDUCED DIABETES-MELLITUS IN RATS

Atrial natriuretic peptide (ANP) infusion increases hematocrit and decreases plasma volume by inducing a transfer of plasma fluid from the vascular to the interstitial compartment. Diabetes mellitus is associated with resistance to the renal actions of ANP. We explored the possibility that the extrarenal responses to ANP may also be altered in the diabetic state by measuring changes in arterial pressure and hematocrit during infusion of ANP (1 mu g.kg(-1).min(-1) for 45 min) into anesthetized, acutely nephrectomized rats 2-3 wk after induction of diabetes from intravenous streptozotocin (STZ) injection (60 mg/kg). Blood glucose was significantly elevated in diabetic rats when compared with control and insulin-treated diabetic rats. Arterial pressure during ANP infusion 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 maximum value of 9.5 +/- 0.9% as a result of the infusion, corresponding to a decrease in plasma volume of 16.3 +/- 1.3%. 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). Reducing the hyperglycemia in diabetic rats by insulin therapy restored the increase in hematocrit in response to ANP (8.5 +/- 1.1%; P < 0.0001 vs. ANP infusion in diabetic rats and P = NS vs. control rats). ANP infusion increased plasma ANP levels to the same extent in the three groups, whereas plasma guanosine 3',5'-cyclic monophosphate (cGMP) was significantly less in diabetic as compared with control and insulin-treated diabetic rats. Acute reduction of hyperglycemia did not restore the ANP-induced increase in hematocrit (1.3 +/- 2.2%; P = NS vs. ANP infusion in diabetic rats). This study demonstrates that 1) the effect of ANP on hematocrit and fluid distribution is blunted in STZ-induced diabetes, while its hypotensive action is preserved, and 2) restoring the glucose levels to normal in diabetic rats by chronic but not by acute insulin treatment normalizes the hemoconcentrating effect of exogenously administered ANP. Such a defect is reflected in a blunted plasma cGMP concentration after ANP infusion in STZ-diabetic rats and may contribute to the altered body fluid physiology in this condition.