Natriuretic Effect of Atrial Natriuretic Peptide in Diabetes Insipidus Rats

Washout of the solute concentration gradient in the renal medullary interstitium has been suggested to play a role in mediating the natriuretic response to atrial natriuretic peptide (ANP). The purpose of this study was to determine the effects of ANP 8–33 on sodium excretion in Brattleboro diabetes insipidus (DI) rats, in which medullary tonicity is known to be decreased as compared to Long-Evans (LE) control rats. Basal urine osmolality (Uosm) was significantly lower in DI rats as compared to LE rats (123 ± 6 vs 673 ± 38 mOsm/kg). Infusion of ANP 8–33 at a rate of 4 μg/kg/hr for 60 min resulted in a significantly greater increase in UnaV (Δ6.1 ± 1.2 vs Δ2.9 ± 0.7 μEq/min) and urine flow (μ40 ± 12 vs μ8 ± 7 μl/min) in the LE rats than in the DI rats. The greater natriuresis occurred in the LE rats despite no significant change in Uosm. Fractional lithium reabsorption (an indicator of proximal sodium reabsorption) decreased similarly in both groups. Infusion of ANP had no effect on mean arterial pressure in LE and DI groups. In summary, infusion of ANP in the DI rat resulted in a significant natriuresis, albeit less than in LE rats. The natriuresis in the LE rats occurred despite no significant change in Uosm. These data suggest that mechanisms other than medullary washout are responsible for the natriuretic effects of ANP.