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Rho-kinase inhibitors protect against neonatal hyperoxia-induced airway hyperreactivity in a rat pup model: Role of prostaglandin F2α.
Beqiraj-Zeqiraj, Qendresa; Thaçi, Qëndrim; Sahiti, Floran; Kovac, Zdenko; Raffay, Thomas M; Sopi, Ramadan B.
Afiliación
  • Beqiraj-Zeqiraj Q; Department of Pathophysiology, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo.
  • Thaçi Q; Pediatric Clinic, University Clinical Centre of Kosovo, Prishtina, Kosovo.
  • Sahiti F; Department of Premedical Courses, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo.
  • Kovac Z; Department of Premedical Courses, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo.
  • Raffay TM; Comprehensive Heart Failure Center, University and University Hospital Würzburg, Würzburg, Germany.
  • Sopi RB; Department of Pathophysiology, School of Medicine, University of Zagreb, Zagreb, Croatia.
Pediatr Pulmonol ; 57(5): 1229-1237, 2022 05.
Article en En | MEDLINE | ID: mdl-35088947
BACKGROUND: Oxygen therapy in preterm neonates is associated with airway hyperreactivity. The role of Rho/Rho-kinase smooth muscle signaling in hyperoxia-induced airway hyperreactivity remains understudied. We hypothesized that inhibition of Rho-kinase will attenuate airway hyperreactivity induced by neonatal hyperoxia. METHODS: Newborn rats were raised in hyperoxia (>95% O2 ) or ambient air (AA) for 7 days. Subgroups were injected with a Rho-kinase inhibitor: Y-27632 (10 mg·kg-1 ·day-1 ) or fasudil (10 mg·kg-1 ·day-1 ), or a FP receptor antagonist - AS604872 (30 mg·kg-1 ·day-1 ). After exposures, tracheal cylinders were prepared for in vitro wire myography. Contraction to methacholine or PGF2α was measured in the presence or absence of tissue-bath Y-27632, fasudil, or AS604872. Lung PGF2α levels, Rho-kinase protein level and Rho-kinase 1 activity were measured by ELISA. RESULTS: Tracheal smooth muscle contraction was significantly greater in hyperoxic compared to AA groups. Both, Y-27632 and fasudil significantly decreased contractility to MCh or PGF2α in hyperoxic groups versus hyperoxic controls (p < 0.001), but did not alter AA group responses. Inhibition of FP receptors attenuated responses to PGF2α . Hyperoxia significantly increased lung PGF2α compared to AA (p < 0.01), but Rho-kinase inhibition did not influence PGF2α level. Rho-kinase protein level (p < 0.001) and activity (p < 0.01), were increased by hyperoxia, but blockade of FP receptor reduced the Rho-kinase 1 activity (p < 0.05) under hyperoxic condition. CONCLUSIONS: This study demonstrates an active role of Rho/Rho-kinase signaling on hyperoxia-induced airway hyperreactivity. These findings suggest that Rho-kinase inhibitors might serve as an effective therapy for hyperoxia-induced airway hyperreactivity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Asma / Hiperoxia Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Pediatr Pulmonol Asunto de la revista: PEDIATRIA Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Asma / Hiperoxia Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Pediatr Pulmonol Asunto de la revista: PEDIATRIA Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos