Beta-adrenergic (isoproterenol) regulation of antidiuretic hormone

Antidiuretic hormone (ADH) and isoproterenol (ISO) both cause renal retention of water when infused iv into animals. It has been suggested that the agents share a common mechanism of action but the current work reveals marked differences in the effect of ISO and ADH on urinary excretion of sodium (ISO produces fall from 50 plus or minus 14 to 3 plus or minus 0.6 mu Eq per 20 min, P greater than 0.0005; ADH causes a fall from 62 plus or minus 14 to 45 plus or minus 9, P greater than 0.05) and creatinine (ISO causes a fall from 157 plus or minus 14 to 71 lus or minus 13, P greater than 0.0005; ADH produces fall from 155 plus or minus 12 to 145 plus or minus 14, P greater than 0.05), which suggest that the actions of the agents may differ. To study that possibility, ISO was infused into normal rats and rats with hereditary diabetes insipidus (DI rats) due to a genetic defect in ADH production. Doses previously used (0.2 mug per kg per min, and doses 10 and 100 fold less were infused. At 0.002 mug per kg per min, urine osmolality in both groups of rats declined (DI rats from 177 plus or minus 22 to 141 plus or minus 13 MOsm per kg, P greater than 0.01, and normals from 162 plus or minus 17 to 142 plus or minus 15 MOsm per kg, P greater than 0.05). At 0.02 mug per kig per min, there was no significant change is osmolality. At 0.02 mug per kig per min, osmolality rose in both groups but the response was significantly blunted in the DI rats (normals: 351 plus or minus 32 to 626 plus or minus 79 mOsm per kg, P greater than 0.005; DI rat: 204 plus or minus 23 to 241 plus or minus 30 P greater than 0.05). It is concluded that intravenous ISO has a dual effect on water excretion; at low doses it is associated with reduced urinary osmolality possibly by direct renal action and at high doses it is associated with antidiuresis by stimulating release of pituitary ADH.