The reproducibility and heritability of individual differences in osmoregulatory function in normal human subjects

The rise in plasma vasopressin produced by infusion of hypertonic saline varies widely among healthy adults. To determine if these interindividual differences are reproducible, we used linear regression to analyze the relationship of plasma vasopressin to plasma osmolality during repeat hypertonic saline infusion in seven normal subjects. The results confirmed that the slope or sensitivity of the relationship differed widely between subjects (0.12 to 1.66 pg/ml/mOsm/kg) and revealed that these differences were highly reproducible. (r = 0.94 on repeat testing). The individual values for osmotic threshold were less variable (280 to 288 mOsm/kg) as well as less clearly reproducible (r = 0.61). To determine whether these differences are genetically influenced, we compared the vasopressin osmolality relationships within seven monozygotic and six dizygotic twin pairs. We found that the threshold and sensitivity values correlated significantly within monozygotes (r = 0.95 and 0.95) but not within dizygotes (r = 0.34 and 0.21). When the osmoregulation of thirst was similarly evaluated, the individual relationships were as variable as for plasma vasopressin, but only the threshold values in monozygotes correlated significantly (r = 0.92). In 80 healthy adults, the frequency distributions of the osmotic threshold and sensitivity of the vasopressin responses were essentially normal. We conclude that the sensitivity for vasopressin secretion as well as the osmotic thresholds for thirst and vasopressin demonstrate significant polygenetic variance among healthy adults.