Renal Fluid and Electrolyte Handling in Streptozotocin-Diabetic Rats

Abstract

Male Sprague-Dawley rats (300–400 g) were made diabetic by an i.p. injection of streptozotocin (STZ, 60 mg/kg in citrate buffer, n = 8) to examine renal function in well-established diabetes mellitus. Vehicle-injected animals (n = 8) acted as controls. The mean weekly total amounts of food taken by control and STZ-diabetic rats did not differ, but diabetic rats exhibited diarrhea and drank more water. STZ-diabetic rats progressively lost weight from the first to the third week but gained weight in the fourth week. At 5 weeks the weight stabilized, plasma glucose concentration was elevated, and this was associated with increased kidney weight. The weekly urine volume from STZ-diabetic rats was elevated throughout the 5-week period of study and this was associated with significantly lower urinary outputs of Na⁺ and higher outputs of K⁺ than those of control animals. After 5 weeks of STZ diabetes, plasma corticosterone and aldosterone concentrations in unanesthetized rats did not differ significantly from values seen in controls. To examine renal function in more detail, groups of Inactin-anesthetized 5-week STZ-diabetic rats (n = 7) and control rats (n = 7) were placed on continuous jugular infusion of 0.077 M NaCl at 150 μL/min for 8.5 h. Following a 3.5-h equilibration period, urine flow and Na⁺, K⁺, and Cl-outputs were determined for the subsequent 5-h period, with mean arterial pressure and glomerular filtration rate (GFR). STZ-diabetic rats voided significantly less of the infused fluid and the urinary excretions of Na⁺ and K⁺ were lower than those of controls. Mean arterial blood pressure and GFR values in STZ-diabetic rats did not differ statistically from those seen in controls. Following hypotonic saline infusion for 8.5 h the levels of aldosterone were elevated significantly (p < 0.01) in STZ-diabetic rats by comparison with control animals (5.36 ± 1.58 nmol/L, n = 7 vs. 2.36 ± 0.12 nmol/L, n = 7). It is concluded that a challenge of hypotonic saline load to rats with 5 weeks of STZ diabetes mellitus elevates plasma aldosterone to reduce the ability to excrete Na⁺.

Key Words:

• Aldosterone
• Diabetes mellitus
• Nephropathy
• Potassium
• Renal function
• Sodium
• Streptozotocin