Renal responsiveness to atrial natriuretic peptide in the noninsulin-dependent diabetic rat

Total body sodium is elevated in noninsulin-dependent diabetes (NIDD) and is implicated in the greater prevalence of systemic hypertension in this population. Given the pivotal role of atrial natriuretic peptide (ANP) in sodium homeostasis, we tested the hypothesis that reduced renal responsiveness to ANP contributes to the sodium retention in NIDD. Two-day old male Sprague-Dawley rats were injected with either streptozotocin (90 mg/kg BW, i.p.; NIDD, n=9) or vehicle (citrate buffer, pH 4.3; control, n=7). At three months of age, diabetes was confirmed by the administration of a glucose tolerance test (2g/Kg, i.p.) which resulted in significantly, greater elevations in blood glucose concentration in the NIDD than control rats. In preparation for renal functional studies, each rat was implanted with femoral vessel cannulae and a bladder catheter, under ether anesthesia. Two days after the surgery, renal excretory responses to a 30 minute infusion of ANP (0.5 μg/min/kg, i.v.) were determined in the conscious rat. This was followed by two, consecutive, 30 minute, recovery periods. Baseline sodium excretion was similar between the groups, while fluid excretion was slightly, albeit significantly, lower in the NIDD rats. The infusion of ANP increased renal fluid and sodium excretion in both groups; however, the natriuretic response was significantly lower in the NIDD than control rats. Thirty minutes after cessation of ANP infusion, renal excretions of fluid and sodium returned towards baseline values in the control rats. In contrast, the NIDD rats maintained elevated fluid and sodium excretions during the recovery periods. Baseline glomerular filtration rate, measured as the rate of ³H-inulin clearance, was similar between the groups and not significantly affected by ANP infusion. Therefore, the natriuretic and diuretic effects of ANP were mediated by reduced tubular reabsorption of fluid and sodium, as indexed by increased fractional excretion of fluid and sodium. In conclusion, the diabetic rat demonstrated a reduced natriuretic response to the infusion of ANP but sustained elevations in fluid and sodium excretions after cessation of ANP infusion.