Unraveling the NO-sGC-cGMP pathway in BPD-associated pulmonary hypertension
Year: 2026
Type: article
Abstract: Preterm infants born before 28 weeks gestation are at high risk for developing bronchopulmonary dysplasia (BPD), a chronic respiratory disorder that is associated with high morbidity and mortality rates in newborns (1).Attenuated alveolar development and impaired microvascular development are widely recognized structural hallmarks of BPD.Current respiratory support for BPD includes supplemental O 2 therapy and/or mechanical ventilation essential for preterm survival.These life saving measures, however, place the preterm infant at increased risk for developing BPD-associated pulmonary hypertension (BPD-PH), wherein abnormal vasculature development leads to a significant increase in vascular resistance and mean pulmonary arterial pressure (>20 mmHg) (2).In severe cases of BPD-PH, inhaled nitric oxide (iNO) is often prescribed as a last resort therapy without clear evidence supporting whether iNO can effectively lower pulmonary vascular resistance in very premature lungs (3).Conversely, in the adult lung, it is clear that iNO can activate soluble guanylyl cyclase (sGC) to produce cyclic guanosine monophosphate (cGMP), which in turn activates cGMPdependent protein kinase (PKG)-mediated vasodilation (4).Hence, the NO-sGC-cGMP pathway is known to promote pulmonary vasodilation, increase blood flow, and improve oxygenation under certain conditions.In this issue of AJP-Heart and Circulatory Physiology, Nguyen et al. (5) examine the role of sGC-mediated increases in cGMP within the context of oxidatively stressed premature lungs.The authors provide new insight into the field as they showcase the effect of sGC signaling using several molecular biological approaches in human embryonic kidney (HEK293T) cells cultured under hyperoxic conditions (75%-95% O 2 ), embryonic mouse lung explants excised at embryonic day 15.5 (E15.5) and subjected to hyperoxia, and the term mouse model of preterm lung injury following chronic 75% O 2 exposure for 14 days.A key experimental benefit of using the term mouse model to model BPD is that this model allows for an integrated physiological evaluation of sGC/cGMP signaling,
Authors: Kimra S. James, My N. Helms
Institution: University of Utah
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7211957754