Vasoactive Intestinal Peptide Reverses The Impaired Airway Relaxation in Neonatal Rats Exposed to Hyperoxia

Neonatal hyperoxia increases contraction and decreases the relaxation of airway smooth muscle (ASM), and the balance between these processes in airways is critical for normal flow of air. Thus, it is important to search for an effective treatment that targets this balance to prevent the airway hyperreactivity. The non-adrenergic- noncholinergic inhibitory system mediators such as vasoactive intestinal peptide (VIP) play an important role in ASM tone. Therefore, we tested the hypothesis that exogenous VIP will reverse the impaired relaxation of tracheal smooth muscle exposed to neonatal hyperoxia. Tracheal cylinders were obtained from Wistar rat pups (P10) exposed to hyperoxia (≥ 95% O2) or room air for seven days. These cylinders were used to study relaxant responses of tracheal smooth muscle (TSM) evoked by electrical field relaxation (EFS) in precontracted tissue (carbachol, 10μM) in absence or presence of a single dose of VIP (50 nM). In addition, the dose-response relaxant effect of VIP (1nM – 1μM) was tested in absence or presence of a VPAC receptor antagonist; a protein kinase A (PKA) inhibitor (Rp-8-CPT-cAMPS); a phosphodiesterase 4 (PDE4) inhibitor (rolipram); or a large-conductance calcium-activated potassium channel blocker (charybdotoxin). The relaxation is expressed as percentage of preconstricted state, and data are presented as mean±s.e.m. Hyperoxic exposure significantly decreased the relaxation of TSM towards EFS, as compared to those obtained from control animals exposed to room air, and these impaired relaxant responses in hyperoxic preparations were significantly reversed in presence of VIP (p<0.01). VIP induced dose-dependent relaxation and the relaxant responses were overcompensated in hyperoxic animals. VPAC antagonist; PKA or PDE4 inhibition significantly reduced VIP-induced relaxation (p<0.05), while blockade of calcium-activated potassium channel did not have significant effect.The results of this study revealed that VIP reverses the impaired relaxation of airway smooth muscle induced by hyperoxic exposure via cAMP/PKA signaling pathway and we speculate that the use of VIP might be an effective therapeutic approach to prevent the airway hyperreactivity induced by hyperoxia. Supported by the Ministry of Education, Science, and Technology of the Republic of Kosovo - Small Research Grants: 2-2459-11. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.