DOES ANGIOTENSIN II RECEPTOR ANTAGONIST LOSARTAN SUPPRESS DRINKING BEHAVIOR IN HEMODIALYSIS PATIENTS?

Angiotensin II (ANG II) is reported to induce drinking behavior in rats with water-deprivation-induced thirst, and cerebroventricular infusion of ANG II blocking agents reportedly attenuates such behavior [[1]]. We sometimes encounter hemodialysis patients who show a large interdialytic weight gain due to drinking excessive amounts of water. Some investigators have reported that angiotensin-converting enzyme (ACE) inhibitors suppress drinking behavior and reduce water intake in hemodialysis patients [2-4]. ANG II receptor antagonists directly block ANG II at the angiotensin I receptor, and ACE inhibitors may similarly block the effect of ANG II. We studied whether the ANG II receptor antagonist Losartan is effective in suppressing drinking behavior in hemodialysis patients.

Seven chronic hemodialysis patients (2 men and 5 women, mean age 58.5 ± 11.8 years) who had not taken any ACE inhibitors for at least 3 months were enrolled in this study. Chronic renal failure was due to chronic glomerulonephritis in 5 patients and to diabetic nephropathy in 2. The mean duration of hemodialysis was 70.3 ± 19.4 months. Six patients had been taking anti-hypertensive drugs other than ACE inhibitors. Following a 10-week observation period, 50 mg of Losartan was given to each patient for 10 weeks (treatment period). Blood samples were collected before and after treatment for assays of serum renin concentration, ACE activity, and ANG II concentration. Protein catabolic rates and sodium intake were also determined.

After Losartan treatment, mean interdialysis body weight gain was significantly reduced in 3 patients (response group). Weight gain was reduced in the other 4 patients (non-response group) but not significantly. Blood and urine analysis findings for both groups are shown in Table 1. ANG II concentrations were significantly lower in the response group than in the non-response group during both the observation and treatment periods. Furthermore, sodium intake of the response group was significantly lower than that of the non-response group during the treatment period. Serum renin concentration, ACE activity, and protein catabolic rate were not changed significantly in either group. Mean interdialysis body weight gain correlated significantly with sodium intake in both groups for the treatment period (Figure 1).

Figure 1. Correlation between sodium intake and interdialysis body weight gain after Losartan treatment. % interdialysis body weight gain: interdialysis body weight gain/dry weight r = 0.746, p < 0.05.

The ANG II receptor antagonist reduced interdialysis body weight gain in a limited number of patients. It is well known that excessive intake of sodium salt stimulates thirst and results in excessive interdialysis body weight gain in hemodialysis patients. Because a lower intake of sodium was observed in our response group, it appears that the effect of Losartan is affected by sodium intake. Because serum ANG II concentrations were significantly high in the non-response group, 50 mg of Losartan may be too little for patients with sodium intake above a certain range. There is another possible explanation for the ineffectiveness of Losartan in the non-response group: There are two types of ANG II receptors in the brain, AT1 and AT2 receptors. Losartan does not block the AT2 receptor. Although the effect of ANG II on thirst via the AT2 receptor is unclear, stimulus of this pathway may induce drinking behavior in some hemodialysis patients.