Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
Purpose: Soluble guanylate cyclase (sGC) is an important receptor for endogenous and exogenous nitric oxide in the pulmonary vasculature, and is a heterodimeric protein composed of α and β subunits. Previous studies have shown decreased sGC activity in pulmonary arteries isolated from lambs with PPHN following surgical ligation of the ductus arteriosus. We hypothesized that altered mRNA expression for one or both subunits might in part explain this decrease in activity. Methods: Surgical ligation of the ductus arteriosus was performed in fetal lambs 9 days prior to delivery at 136 days gestation (term = 140-145 days). sGC mRNA was quantitated by ribonuclease protection assays in pulmonary arteries (PA) and veins (PV) isolated from PPHN lambs (n=3) and their twin controls (n=3) using 32P labeled antisense probes for the α and β subunits of sGC. Additional samples were obtained from fetal lambs at 127 days gestation (n=2), the age at which the ligation is performed. Results:32P labeled transcripts of Hind III linearized plasmid, a TA Cloning Vector(PCR™III) containing PCR α or β insert, yielded hybridized products of 257 bases corresponding to the α subunit and 185 bases for the β subunit. The table shows that expression for the α-sGC subunit increased by 64 fold in PA and 15 fold in PV between 127 and 136 days gestation. Similarly, expression for the β subunit increased by 14 fold in PA and 5 fold in PV during the same time period. Expression for the α subunit in PA from hypertensive lambs was decreased by 5 fold (p<0.05) compared to controls, but was not significantly altered in PV. No significant changes were observed for expression of the β subunit in PA or PV from PPHN lambs. Conclusion: The α andβ sGC subunits are developmentally coregulated in pulmonary vessels during late gestation in the fetal lamb. We speculate that there is differential regulation of the α and β subunits, and that regulation of the α subunit is altered in PPHN.
