Abstract 15715: Decreased Serum Osmolality Augments the Closure of the Ductus Arteriosus in Neonates
Introduction: The ductus arteriosus (DA) must be closed after birth for establishment of adult circulation. We found that serum osmolality significantly decreased early after birth in rats, and that the hypoosmolality sensor transient receptor potential melastatin (TRPM) 3 was highly expressed in the rat DA compared to the aorta.
We assessed the hypothesis that serum hypoosmolality promoted closure of the DA via TRPM3.
Methods: Human serum osmolality in late (28-35 weeks’ gestation, n=35, LPI) and early preterm infants (24-27 weeks’ gestation, n=28, EPI) was analyzed by freezing point depression osmometry. Intracellular calcium was assessed by Fura-2 in smooth muscle cells from the rat DA on day 21 of gestation (DASMCs). Vasoconstriction was measured by a wire myograph. Rapid total body freezing method was used to examine in-vivo vasoconstriction.
Results: Serum osmolality was decreased 2 h after birth in LPI by 3.2±0.8% (p<0.001), but not in EPI. During the first 24 h after birth, serum osmolality was greatly elevated in EPI (16.7±3.2mOsm/kg, p<0.001), but such effect was moderate in LPI (4.7±2.1mOsm/kg, p<0.05). In EPI with patent DA (PDA), elevation of serum osmolality during the first 24 h was significantly greater than in EPI without PDA (21.9±3.1 and 10.1±3.6, p<0.05, n=13-15). We then examined the effect of change in osmolality on the rat DA. In DASMCs, hypoosmolality (270mOsm/kg) increased intracellular calcium level by 6.6% of basal 340/390 ratio (p<0.01, n=6), which was attenuated by TRPM3-targeted siRNA by 48.7% (p<0.01, n=12). Hypoosmolality (270 and 250mOsm/kg) induced contraction in rat DA (17.4% and 29.8% of KCl, respectively, p<0.01, n=8), but not in the rat aorta. Furthermore, the TRPM3 activator pregnenolone sulfate (200μM) induced contraction of the rat DA (39.4% of KCl, p<0.01, n=6). Conversely, when serum osmolality was kept higher to 335mOsm/kg by intra-peritoneal injection of 7.2% hypersaline, DA closure was partially inhibited by 35% compared to 0.9% saline control in vivo (p<0.001, n=5).
Conclusions: These results suggest that decrease of serum osmolality promotes DA closure via TRPM3 and that increase in osmolality dilates the DA.
Maintaining proper levels of serum osmolality may improve the therapeutic outcome of PDA in EPI.
- © 2013 by American Heart Association, Inc.