Abstract 171: Plasma Hypoosmolarity After Birth Promotes Closure of the Ductus Arteriosus
Background: Changes in environmental conditions after birth, such as increased oxygen tension, are known to regulate the closure of the ductus arteriosus (DA). We previously found that plasma osmolarity was significantly decreased early after birth in rats, and that Transient Receptor Potential Melastatin (TRPM) 3, a hypoosmolarity sensor, was highly expressed in the rat DA compared to the aorta. We assessed the hypothesis that plasma hypoosmolarity regulated tension of the DA via TRPM3.
Methods: Fura-2 assay was used to evaluate the change in intracellular calcium [Ca2+]i in vascular smooth muscle cells (SMCs). Tension of vascular rings was measured by a wire myograph system. Rapid whole-body freezing method was used to examine vasoconstriction in rat in vivo. Plasma osmolarity of human preterm infants was analyzed by freezing point depression osmometry.
Results: We found that [Ca2+]i was increased by hypoosmolarity (270mOsm/kg) in SMCs isolated from the rat DA (DASMCs) compared to aortic SMCs (31.3% vs. 8.5% of basal 340/390 ratio P<0.01, n=6). When DASMCs were treated with siTRPM3, hypoosmolarity-induced [Ca2+]i elevation was attenuated by 48.7% (P<0.01, n=6). Hypoosmolarity (270 and 250mOsm/kg) increased the tension of rat DA (17.4% and 29.8% of 120mM of KCl, respectively, P<0.01, n=8). Moreover, a TRPM3 activator pregnenolone sulfate (200μ M) induced contraction of the rat DA (39.4% of KCl P<0.001, n=6). Conversely, when plasma osmolarity was kept higher to 322mOsm/kg by intra-peritoneal injection of 5.4% hypersaline, the DA closure was partially inhibited by 13% compared to 0.9% saline injection in vivo (P<0.05, n=11). Plasma osmolarity was decreased 2 h after birth in late preterm infants (28-35weeks’ gestation) (3.2±0.8 % reduction of cord blood, P<0.001, n=35), but not in early preterm infants (24-27weeks’ gestation) (1.1±1.3 % reduction of cord blood, NS, n=17). Furthermore, plasma osmolarity of patent DA (PDA) patients recovered to the adult level by the 2nd day of life while it still remained low in non PDA patients.
Conclusions: These results suggest that plasma hypoosmolarity after birth promotes DA closure via TRPM3 and that keeping the plasma osmolarity within proper levels during early neonatal period would be important for DA closure.
- © 2012 by American Heart Association, Inc.