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 microL/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+.

The effects of 3 consecutive days of oral chloroquine (1 mg/100 g body weight) on kidney function and blood pressure were studied in male Sprague-Dawley rats that were challenged with hypotonic saline infusion 24 h after the last chloroquine administration. The rats were anesthetized with Inactin [5 ethyl-5-(1'-methylpropyl)-2-thiobarbiturate, Byk Gulden] and continuously infused with 0.077 M NaCl for 8 h; urine flow and electrolyte excretion rates were monitored during the last 5 h. Blood pressure and glomerular filtration rates were also measured. Kidney function was compromised in chloroquine-treated rats, which retained significantly more of the infused Na+ and Cl- by comparison to control-vehicle-treated rats. Throughout the experimental period, chloroquine-treated rats exhibited low blood pressure (80 mm Hg vs. 127 mm Hg) which was associated with low glomerular filtration rate. The plasma aldosterone concentrations were significantly (p < 0.01) elevated in rats pretreated with chloroquine at the end of the 8-h infusion of hypotonic saline, but corticosterone levels were significantly (p < 0.01) lower in the treated rats. It is concluded that chloroquine administration impairs kidney function, resulting in inappropriate Na+ and Cl- retention. This effect is likely to be mediated via chloroquine-induced increases in plasma aldosterone concentration and lowering of GFR.

No abstract

SUMMARYThe possibility of an interaction between oxytocin and aldosterone to influence renal Na+ excretion was investigated in Inactin-anaesthetized male Sprague-Dawley rats. Endogenous plasma concentrations of aldosterone were suppressed by either adrenalectomy or bicarbonate infusion. The effects of 2 h intravenous administration of oxytocin (0-04 pmol/min) and/or aldosterone (42 pmol/min) on renal Na+ handling were studied in 0077 M NaCl-infused adrenalectomized (Adx) rats and groups of intact animals that were infused with 0 077 M NaHCO3. Aldosterone alone significantly (P < 0 01) reduced Na+ excretion from pretreatment peak value of 5 0 + 1 0 to 1 5 + 0 4 flmol/min in Adx animals (n = 8) and 9 2 + 1 2 to 5 2 + 12 ,umol/min in NaHCO3-infused rats (n = 8) by 2 h after the start of administration. However, combined administration of aldosterone and oxytocin was associated with a significantly (P < 0 01) increased Na+ excretion rate from a peak pretreatment value of 68 + 07 ,tmol/min to a peak value of 11 5 ±1 ,amol/min by 1 h 40 min after the start of treatment in Adx rats (n = 7). In bicarbonate-infused rats (n = 8) Na+ excretion rose within 20 min of the start of treatment from a pretreatment peak of 9 0 + 0 8 ,tmol/min to a peak value of 13 5 + 0 8 ,tmol/min in response to combined hormone administration. In conclusion, we have shown that concomitant administration of aldosterone and oxytocin increased the rate of excretion of Na+ in two different preparations, which supports the idea of an interaction between the steroid and oxytocin to promote Na+ loss.