SOMATOSTATIN AS A MODULATOR OF DISTAL NEPHRON WATER PERMEABILITY

1. Experiments in vivo and in vitro were performed in the rat to defin e the role of somatostatin in modulating the hydro-osmotic action of a rginine vasopressin. 2. Somatostatin had a biphasic effect on basal co llecting duct diffusional water permeability with 10(-9) mol/l somatos tatin producing a 14% reduction in permeability, whereas concentration s of 10(-6) and 10(-5) mol/l significantly increased basal water perme ability by 13% and 22%, respectively. Somatostatin (10(-9) mol/l) also inhibited the increase in water permeability produced by arginine vas opressin, although this inhibitory effect was reduced by a 10-fold inc rease in arginine vasopressin concentration (5 ng/ml). 3. In the anaes thetized water-diuretic rat, low dose somatostatin (60 mug/h) increase d free water clearance by 23% (P<0.01), whereas increasing the somatos tatin concentration (600 mug/h) produced a transitory 40% fall in free water clearance (P<0.01). As in the experiment in vitro, somatostatin inhibited the action of arginine vasopressin, although a very high co ncentration of arginine vasopressin (250 ng/h) partly overcame this ef fect. 4. Glomerular filtration rate and renal electrolyte excretion (s odium, potassium, calcium, magnesium) were not altered by somatostatin , although renal inorganic phosphate excretion was increased. The papi llary solute gradient was unaltered by somatostatin. 5. These results suggest that circulating somatostatin may have a physiological role in modulating distal nephron water transport with a low concentration di rectly inhibiting and a high concentration facilitating water transpor t. There is also evidence of competitive binding between somatostatin and arginine vasopressin which antagonizes the hydro-osmotic action of arginine vasopressin.