Reciprocal regulation of plasma apelin and vasopressin by osmotic stimuli

Abstract

Apelin is a neuropeptide that co-localizes with vasopressin (AVP) in magnocellular neurons and is involved in body fluid homeostasis. Osmotic stimuli have opposite effects on the regulation of apelin and AVP secretion in animal models, but whether this is true in humans is unknown. This study investigated the relationship among osmolality, apelin, and AVP in 10 healthy men after infusion of hypertonic saline or loading with water to increase and decrease plasma osmolality, respectively. Increasing plasma osmolality was accompanied by a parallel, linear increase in plasma AVP concentration and by a decrease in plasma apelin concentration. In contrast, decreasing plasma osmolality by water loading reduced plasma AVP concentration and rapidly increased plasma apelin concentration. These findings suggest that regulation of apelin secretion contributes to the maintenance of body fluid homeostasis.

Figure 1.

Reverse-phase HPLC analysis of apelin-IR in human plasma. A human plasma sample was chromatographed on a Vydac C4 column, and the immunoreactive material contained in the HPLC fractions was quantified by RIA. This chromatogram is representative of four independent experiments giving the following percentage of each apelin fragment: pE13F, 30 ± 13%, K17F, 56 ± 12%, and apelin 36, 14 ± 7%. The dotted line indicates the acetonitrile gradient. The arrows indicate the elution positions of the reference peptides.

Figure 2.

Effects of a 2-h hypertonic saline infusion (0.85 M, 0.06 ml/kg per min) on plasma osmolality (A) and plasma AVP (B) and apelin (C) concentrations. Plasma osmolality and apelin are expressed as means ± SEM. Plasma AVP is expressed as medianand IQR. The ANOVA for repeated measurements over time on day 1 with a modeling covariance structure within subjects was significant for all three variables. Pair-wise comparisons were tested using the Dunnett adjustment procedure for multiple tests comparing all time points with baseline level at 9:00 a.m. on day 1. *P < 0.05; **P < 0.01; ***P < 0.001 versus baseline (9:00 a.m. on day 1).

Figure 3.

Linear correlations between plasma AVP concentration and plasma osmolality (A), between plasma apelin concentration and plasma osmolality (B), and between plasma apelin concentration and plasma AVP concentration (C) during a 2-h hypertonic saline infusion (0.85 M, 0.06 ml/kg per min).

Figure 4.

Effects of a 2-h hypertonic saline infusion (0.85 M, 0.06 ml/kg per min ○) and a 20-ml/kg water load within 30 min (•) on the plasma apelin/AVP ratio. Data are expressed as medians and IQR. The ANOVA for repeated measurements over time on day 1 was significant in each group. Then pair-wise comparisons were tested using the Dunnett adjustment procedure for multiple tests comparing all time points to baseline level at 9:00 a.m. on day 1. *P < 0.05; **P < 0.01; ***P < 0.001 versus baseline (9:00 a.m. on day 1).

Figure 5.

(A) Time course of observed (•) and predicted (○) plasma apelin concentration during the hypertonic saline infusion. The equation of the regression line between plasma apelin and plasma osmolality between times 0 and 80 min was then used to predict the curve for plasma apelin between time 80 and time 120 min. (B) Plot of the absolute difference between the observed and the predicted plasma apelin values (left axis, ⋄) and of the relative increase in estimated extracellular fluid volume (right axis, ♦). The observed and predicted values diverged once estimated ECFV had increased by 12 to 15%. Data are means ± SEM.

Figure 6.

Effects of a 20-ml/kg water load within 30 min on plasma osmolality (A) and plasma AVP (B) and apelin (C) concentrations. Plasma osmolality and apelin are expressed as means ± SEM. Plasma AVP is expressed as median and IQR. The ANOVA for repeated measurements over time on day 1 was significant for all three parameters. Then pair-wise comparisons were tested using the Dunnett adjustment procedure for multiple tests comparing all time points with baseline level at 9:00 a.m. on day 1. *P < 0.05; **P < 0.01; ***P < 0.001 versus baseline (9:00 a.m. on day 1).