Apelin-13 Regulates Vasopressin-Induced Aquaporin-2 Expression and Trafficking in Kidney Collecting Duct Cells.

BACKGROUND/AIMS: Apelin and its G protein-coupled receptor APJ (gene symbol Aplnr) are strongly expressed in magnocellular vasopressinergic neurons suggesting that the apelin/APJ system plays a key role at the central level in regulating salt and water balance by counteracting the antiduretic action of vasopressin (AVP). Likewise, recent studies revealed that apelin exerts opposite effects to those of vasopressin induced on water reabsorption via a direct action on the kidney collecting duct. However, the underlying mechanisms of the peripheral action of apelin are not clearly understood. Here, we thus investigated the role of the apelin/APJ system in the regulation of water balance in the kidney, and more specifically its involvement in modulating the function of aquaporin-2 (AQP2) in the collecting duct. METHODS: Mouse cortical collecting duct cells (mpkCCD) were incubated in the presence of dDAVP and treated with or without apelin-13. Changes in AQP2 expression and localization were determined by immunoblotting and confocal immunofluorescence staining. RESULTS: Herein, we showed that the APJ was present in mpkCCD cells. Treatment of mpkCCD with apelin-13 reduced the cAMP production and antagonized the AVP-induced increase in AQP2 mRNA and protein expressions. Immunofluorescent experiments also revealed that the AVP-induced apical cell surface expression of AQP2, and notably its phosphorylated isoform AQP2-pS269, was considerably reduced following apelin-13 application to mpkCCD cells. CONCLUSION: Our data reinforce the aquaretic role of the apelin/APJ system in the fine regulation of body fluid homeostasis at the kidney level and its physiological opposite action to the antiduretic activity of AVP.

Effects of hypoxia and hypercapnia on nonnutritive swallowing in newborn lambs.

The aim of the present study was to investigate the effect of hypercapnia and hypoxia on apnea and nonnutritive swallowing (NNS) frequency, as well as on the coordination between NNS and phases of the respiratory cycle in newborn lambs, while taking into account the potential effects of states of alertness. Six lambs were chronically instrumented for recording electroencephalogram, eye movements, diaphragm and thyroarytenoid muscle (a glottal adductor) activity, nasal airflow, and electrocardiogram. Polysomnographic recordings were performed in nonsedated lambs exposed to air (control), 10% O(2), and 5% CO(2) in a random order at 3, 4, and 5 days of age. Although hypercapnia decreased apnea frequency in wakefulness and active sleep (P = 0.002 vs. air and hypoxia), hypoxia had no significant effect on apnea. In addition, although hypercapnia increased NNS frequency during wakefulness and quiet sleep (P < 0.005 vs. air and hypoxia), hypoxia tended to decrease NNS frequency. Finally, only hypercapnia altered NNS-breathing coordination by increasing NNS at the transition from inspiration to expiration (ie-type NNS; P < 0.001 vs. air and hypoxia). In conclusion, whereas hypercapnia increases overall NNS frequency by specifically increasing ie-type NNS, hypoxia has the inverse tendency. Results were identical in all three states of alertness.