Does Aging Impair Pulmonary Artery Reactivity to Hypoxia and Nitric Oxide?

Aging is associated with a higher prevalence of pulmonary hypertension, a relationship that may stem from functional and structural alterations within the pulmonary vasculature. Episodes of hypoxaemia—such as those resulting from intermittent pharyngeal collapse during sleep—also become more common with advancing age and may further contribute to pulmonary vascular dysfunction by provoking vasoconstriction and promoting vascular remodeling. Together, these factors likely compound age-related vulnerability in pulmonary vascular regulation. However, it remains unclear whether healthy aging independently impairs pulmonary vascular function or alters vascular responsiveness to fluctuations in oxygen availability. Objective: To determine whether aging modifies pulmonary vascular endothelial function and its responsiveness to changes in oxygen tension. Hypothesis: Aging will attenuate the pulmonary artery vasodilatory response to inhaled nitric oxide—a selective pulmonary vasodilator and marker of pulmonary endothelial function—and blunt hypoxic pulmonary vasoreactivity. Methods: Eight healthy young adults (YA: 5 females; 25 ± 3 yr; 65 ± 11 kg; 23 ± 4 kg/m 2 ) and five healthy older adults (OA: 4 females; 71 ± 5 yr; 70 ± 20 kg; 25 ± 5 kg/m 2 ) completed echocardiographic assessments of pulmonary artery systolic pressure (PASP) during the last minute of 10-min normoxia and isocapnic hypoxia (FiO 2 ≈ 0.10) trials. Inhaled nitric oxide (40 ppm) was administered during the final 5 min of each trial. PASP was quantified from the peak systolic tricuspid regurgitant gradient plus estimated right atrial pressure derived from inferior vena cava collapsibility. Beat-to-beat arterial pressure, arterial oxygen saturation (SpO 2 ), and end-tidal PO 2 and PCO 2 were recorded continuously. Results: Beat-to-beat arterial pressure, SpO 2 , end-tidal PO 2 , and PCO 2 did not differ between conditions or age groups, indicating stable ventilatory and systemic physiological states. PASP increased during isocapnic hypoxia in both YA (16 ± 6 → 19 ± 6 mmHg, p = 0.059) and OA (25 ± 11 → 34 ± 18 mmHg, p = 0.036), with a greater hypoxic vasoconstrictor response in OA compared with YA (OA: +7 ± 2 mmHg vs. YA: +2 ± 2 mmHg, p = 0.042). Inhaled nitric oxide reduced PASP during both normoxia (OA: −7 ± 7 mmHg vs. YA: −4 ± 2 mmHg, p = 0.268) and hypoxia (OA: −11 ± 8 mmHg vs. YA: −11 ± 11 mmHg, p = 0.268), with no age-related differences in nitric oxide responsiveness. Nitric oxide–mediated vasodilation also did not differ between normoxia and hypoxia within either age group (p > 0.05). Conclusion: Despite a greater hypoxic vasoconstrictor response in older adults, pulmonary artery vasodilation to inhaled nitric oxide and overall vascular responsiveness to changes in oxygen tension were preserved, suggesting that healthy aging does not diminish pulmonary endothelial function. Funding: Supported by the Arthur C. Guyton Award from the American Physiological Society, the American Heart Association (Grant 24CDA1273371), and the Mallinckrodt Pharmaceuticals Investigator Initiated Research (IIR-USA-011253). This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.