Pituitary Adenylate Cyclase Activating Peptide Restores Hyperoxia-Impaired Relaxation of Tracheal Smooth Muscle in Neonatal Rats

Autor: Qëndrim Thaçi, Islam Kryeziu, Shkëlzen Reçica, Qëndresa Beqiraj-Zeqiraj, Kemajl Bislimi, Mitko Mladenov, Ramadan Sopi
Rok vydání: 2023
Předmět:
Zdroj: Physiology. 38
ISSN: 1548-9221
1548-9213
Popis: Neonatal hyperoxia induces airway hyperreactivity by potentiating contractile responses and impairing the relaxation of airway smooth muscle (ASM). Maintenance of balance between these processes in airways is critical for normal flow of air, and non-adrenergic- noncholinergic inhibitory system is an important component of airway smooth muscle tone. Therefore, we tested the hypothesis that exogenous pituitary adenylate cyclase activating peptide (PACAP) will restore the impaired relaxant responses 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 ASM evoked by electrical field relaxation (EFS) in precontracted tissues (carbachol, 5x10μM) in absence or presence of a single dose of PACAP (50 nM). In addition, the dose-response relaxant effect of PACAP (1nM – 1μM) was tested in absence or presence of a PAC1 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 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 PACAP (p 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.
Databáze: OpenAIRE