Vasoactive Intestinal Peptide Attenuates Hyperoxia-Induced Airway Hyperreactivity in Neonatal Rats.

التفاصيل البيبلوغرافية
العنوان: Vasoactive Intestinal Peptide Attenuates Hyperoxia-Induced Airway Hyperreactivity in Neonatal Rats.
المؤلفون: Thaçi, Qëndrim1, Reçica, Shkëlzen2, Kryeziu, Islam2, Sopi, Ramadan B.1 ramadan.sopi@uni-pr.edu
المصدر: International Conference on New Achievements in Science, Technology & Arts (ICNA-STA). 2023, p93-93. 1p.
مستخلص: 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 attenuate the contraction and promote 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 contractile responses evoked by carbachol (10-8 - 10-4 M) and relaxant responses of ASM 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 a percentage of pre-constricted state, and the data are presented as mean/s.e.m. Hyperoxic exposure significantly decreased the relaxant responses of ASM towards EFS, as compared to those obtained from control animals exposed to room air, and these reduced relaxant responses in hyperoxic tissues were significantly reversed in presence of VIP (p<0.01). VIP induced dosedependent 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 a significant effect. The results of this study revealed that VIP attenuates airway hyperreactivity and reverses the impaired relaxation of airway smooth muscle induced by hyperoxic exposure via cAMP/PKA signaling pathway. We speculate that the use of VIP might be an effective therapeutic approach to prevent the airway hyperreactivity induced by hyperoxia. [ABSTRACT FROM AUTHOR]
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