Influence of plasma amino acid level on vasopressin secretion

Vasopressin (VP) is known to be elevated in patients with diabetes mellitus (DM). While the influence of acute hyperglycemia has been ruled out, the mechanism or the osmotically active compound responsible for the increase in VP secretion is still not elucidated. Because the plasma level of several amino acids (AAs) is increased in DM, we evaluated whether AAs could represent an effective osmotic stimulus for VP secretion.

In a cross-over study, eight healthy volunteers randomly received an infusion of isotonic saline (control) or mixed AA solution, i.v., at a low or a high rate (2 or 4.5 mg/min/kg BW, respectively). Plasma VP (P(VP)) was measured for two hours before and three hours during AA or control infusion.

AA infusion induced a dose-dependent elevation in plasma AA concentration but did not alter P(VP). However, effective plasma osmolality (P(osm)) (osmolality minus urea concentration) remained unchanged because a concommittant fall in plasma sodium concentration (P(Na)), likely due to sodium-linked uptake of AA in peripheral cells, compensated for the rise in plasma AA.

The stability of effective P(osm) may explain the lack of change observed in P(VP). Because sodium is a very efficient stimulus for VP secretion, it may be assumed that the fall in P(Na) occurring during AA infusion should have reduced VP secretion and thus P(VP). In this setting, the stability of P(VP) suggests that AAs induced an increase in VP secretion which counterbalanced the fall attributable to the decrease in P(Na). In conclusion, in acute experiments, AAs seem to represent an effective stimulus for VP secretion, almost equally potent as sodium. Further studies are needed to evaluate their contribution to the high P(VP) seen in the chronic setting of DM.