c-Kit deficiency impairs nitric oxide signaling in smooth muscle cells
| Autor: | Roberta M. Lassance-Soares, Diana R. Hernandez, Roberto I. Vazquez-Padron, Boris L Rodriguez, Zachary M. Zigmond, Miguel G. Rojas, Laisel Martinez |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Myocytes Smooth Muscle Biophysics Blood Pressure Prostacyclin Vasodilation Nitric Oxide Biochemistry Article Nitric oxide Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Internal medicine medicine Animals Sodium Chloride Dietary Molecular Biology Mesenteric arteries Electrical impedance myography Chemistry Arteries Cell Biology Proto-Oncogene Proteins c-kit 030104 developmental biology medicine.anatomical_structure Endocrinology 030220 oncology & carcinogenesis Prostaglandins Endothelium Vascular Soluble guanylyl cyclase Signal Transduction medicine.drug Artery |
| Zdroj: | Biochem Biophys Res Commun |
| ISSN: | 0006-291X |
| Popis: | Introduction Receptor tyrosine kinases have been implicated in various vascular remodeling processes and cardiovascular disease. However, their role in the regulation of vascular tone is poorly understood. Herein, we evaluate the contribution of c-Kit signaling to vasoactive responses. Methods The vascular reactivity of mesenteric arteries was assessed under isobaric conditions in c-Kit deficient (KitW/W−v) and littermate control mice (Kit+/+) using pressure myography. Protein levels of soluble guanylyl cyclase beta 1 (sGCβ1) were quantified by Western blot. Mean arterial pressure was measured after high salt (8% NaCl) diet treatment using the tail-cuff method. Results Smooth muscle cells (SMCs) from c-Kit deficient mice showed a 5-fold downregulation of sGCβ1 compared to controls. Endothelium-dependent relaxation of mesenteric arteries demonstrated a predominance of prostanoid vs. nitric oxide (NO) signaling in both animal groups. The dependence on prostanoid-induced dilation was higher in c-Kit mutant mice than in controls, as indicated by a significant impairment in vasorelaxation with indomethacin with respect to the latter. Endothelium-independent relaxation showed significant dysfunction of NO signaling in c-Kit deficient SMCs compared to controls. Mesenteric artery dilation was rescued by addition of a cGMP analog, but not with a NO donor, indicating a deficiency in cGMP production in c-Kit deficient SMCs. Finally, c-Kit deficient mice developed higher blood pressure on an 8% NaCl diet compared to their control littermates. Conclusion c-Kit deficiency inhibits NO signaling in SMCs. The existence of this c-Kit/sGC signaling axis may be relevant for vascular reactivity and remodeling. |
| Databáze: | OpenAIRE |
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