LACK OF ANTIDIURETIC ACTIVITY OF LANREOTIDE IN THE DIABETES-INSIPIDUSRAT

Lanreotide is a somatostatin analog which possesses antidiuretic activ ity in the rat. To determine whether vasopressin participates in the a ntidiuretic response to lanreotide, experiments were performed with di abetes insipidus (DI) rats homozygous for vasopressin deficiency. Lanr eotide significantly increased urine osmolality and decreased urine vo lume and free water clearance during the 2-h period after injecting 40 0 mu g/kg s.c. in 12 awake Wistar-Kyoto rats that were undergoing wate r diuresis. Although lanreotide decreased serum growth hormone levels (24.2 +/- 6.1 vs. 0.9 +/- 0.1 ng/ml, P < .01), administration of recom binant human growth hormone (1 mg/kg s.c.) did not affect the renal re sponse. Lanreotide (200 mu g/kg s.c.) also significantly increased uri ne osmolality and free water reabsorption and tended to decrease urine volume in 15 water-loaded Long-Evans rats. In contrast, lanreotide (2 00 or 400 mu g/kg s.c.) did not affect urine osmolality, urine volume or free water clearance when administered acutely or chronically to DI rats. These results suggest that vasopressin plays a role in the rena l response to lanreotide in the rat.