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

Atrial natriuretic peptide (ANP) infusion increases hematocrit and dec reases plasma volume by inducing a transfer of plasma fluid from the v ascular to the interstitial compartment. Diabetes mellitus is associat ed with resistance to the renal actions of ANP. We explored the possib ility that the extrarenal responses to ANP may also be altered in the diabetic state by measuring changes in arterial pressure and hematocri t during infusion of ANP (1 mu g.kg(-1).min(-1) for 45 min) into anest hetized, acutely nephrectomized rats 2-3 wk after induction of diabete s from intravenous streptozotocin (STZ) injection (60 mg/kg). Blood gl ucose was significantly elevated in diabetic rats when compared with c ontrol and insulin-treated diabetic rats. Arterial pressure during ANP infusion decreased similarly in control, diabetic, and insulin-treate d diabetic rats (by 7.6 +/-: 1.6, 9.6 +/- 1.9, and 8.2 +/- 2% respecti vely; all P < 0.002). In control rats, hematocrit increased progressiv ely to a maximum value of 9.5 +/- 0.9% as a result of the infusion, co rresponding to a decrease in plasma volume of 16.3 +/- 1.3%. In contra st, the ANP-induced increase in hematocrit was markedly blunted in dia betic rats (1.6 +/- 0.8%; P < 0.0001 vs. ANP infusion in control rats) . Reducing the hyperglycemia in diabetic rats by insulin therapy resto red 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 thr ee groups, whereas plasma guanosine 3',5'-cyclic monophosphate (cGMP) was significantly less in diabetic as compared with control and insuli n-treated diabetic rats. Acute reduction of hyperglycemia did not rest ore the ANP-induced increase in hematocrit (1.3 +/- 2.2%; P = NS vs. A NP infusion in diabetic rats). This study demonstrates that 1) the eff ect of ANP on hematocrit and fluid distribution is blunted in STZ-indu ced diabetes, while its hypotensive action is preserved, and 2) restor ing the glucose levels to normal in diabetic rats by chronic but not b y acute insulin treatment normalizes the hemoconcentrating effect of e xogenously administered ANP. Such a defect is reflected in a blunted p lasma cGMP concentration after ANP infusion in STZ-diabetic rats and m ay contribute to the altered body fluid physiology in this condition.