Intermittent Hypoxia Alters Sensory Nerve Mediated Vasoreactivity in Mouse Pulmonary Arteries

Obstructive sleep apnea is a prevalent condition which increases the risk for a variety of cardiovascular diseases. Intermittent hypoxia (IH) associated with sleep apnea leads to pulmonary hypertension. Long-term IH alters neuronal function, however, the effects of IH on sensory nerve mediated vasoreactivity have not been defined. We hypothesized that changes in sensory (peptidergic) signaling enhance vasomotor tone following IH. To test this hypothesis, we evaluated vasoreactivity to the sensory neurotransmitters calcitonin gene related peptide (CGRP) and substance P in isolated, pressurized (16 cmH 2 O) pulmonary arteries (100-150 µm diameter) from male C57BL/6J mice exposed to cycles of IH (90s 6% O 2 / 90s room air) or room aim for 12 hr/day for 8 weeks. Changes in smooth muscle V m during exposure to peptidergic agents were continuously recorded using intracellular microelectrodes. Vasodilation to CGRP (10 -10 -10 -6 M) in pulmonary arteries preconstricted with uridine triphosphate (UTP, 5 µM; EC 50 ) was significantly (p<0.05) impaired in vessels from IH mice. Consistently, IH reduced hyperpolarization to CGRP in smooth muscle cells from pulmonary arteries. In vessels from mice exposed to room air, substance P (10 -9 -10 -5 M) initially evoked a vasodilatory response that transitioned into a vasoconstrictor response at higher concentrations. IH significantly impaired vasodilation and augmented vasoconstriction to substance P and led to a leftward shift in the transition from vasoconstrictor to vasodilatory effects. In a similar fashion, vessels from IH mice had impaired smooth muscle cell hyperpolarization at lower concentrations of substance P and enhanced depolarization at higher concentrations. We conclude that IH associated with sleep apnea enhances vasomotor tone mediated by sensory nerves in pulmonary arteries from mice. AHA CDA#931652; NIH HL166617 This abstract was presented at the American Physiology Summit 2025 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.