Senescent murine femoral arteries undergo vascular remodelling associated with accelerated stress‐induced contractility and reactivity to nitric oxide
| العنوان: | Senescent murine femoral arteries undergo vascular remodelling associated with accelerated stress‐induced contractility and reactivity to nitric oxide |
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| المؤلفون: | Doris Metzler, Lubomir T. Lubomirov, Gabriele Pfitzer, Oliver Ritter, Monique Jänsch, Olaf Grisk, Mechthild M. Schroeter, Maria Bust, Symeon Papadopoulos, Jürgen Hescheler |
| المصدر: | Basic & Clinical Pharmacology & Toxicology. 130:70-83 |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | medicine.medical_specialty, Phosphatase, Vascular Remodeling, Nitric Oxide, Toxicology, Polymerase Chain Reaction, Nitric oxide, Vascular remodelling in the embryo, Contractility, Mice, Myosin-Light-Chain Phosphatase, chemistry.chemical_compound, Vascular Stiffness, Stress, Physiological, Internal medicine, Myosin, Cyclic GMP-Dependent Protein Kinases, medicine, Animals, Nitric Oxide Donors, Protein phosphorylation, RNA, Messenger, Phosphorylation, Cyclic GMP, Pharmacology, Electrical impedance myography, Age Factors, General Medicine, Femoral Artery, Mice, Inbred C57BL, Endocrinology, chemistry |
| الوصف: | This work explored the mechanism of augmented stress-induced vascular reactivity of senescent murine femoral arteries (FAs). Mechanical and pharmacological reactivity of young (12-25 weeks, y-FA) and senescent (>104 weeks, s-FAs) femoral arteries was measured by wire myography. Expression and protein phosphorylation of selected regulatory proteins were studied by western blotting. Expression ratio of the Exon24 in/out splice isoforms of the regulatory subunit of myosin phosphatase, MYPT1 (MYPT1-Exon24 in/out), was determined by polymerase chain reaction (PCR). While the resting length-tension relationship showed no alteration, the stretch-induced-tone increased to 8.3 ± 0.9 mN in s-FA versus only 4.6 ± 0.3 mN in y-FAs. Under basal conditions, phosphorylation of the regulatory light chain of myosin at S19 was 19.2 ± 5.8% in y-FA versus 49.2 ± 12.6% in s-FA. Inhibition of endogenous NO release raised tone additionally to 10.4 ± 1.2 mN in s-FA, whereas this treatment had a negligible effect in y-FAs (4.8 ± 0.3 mN). In s-FAs, reactivity to NO donor was augmented (pD2 = -4.5 ± 0.3 in y-FA vs. -5.2 ± 0.1 in senescent). Accordingly, in s-FAs, MYPT1-Exon24-out-mRNA, which is responsible for expression of the more sensitive to protein-kinase G, leucine-zipper-positive MYPT1 isoform, was increased. The present work provides evidence that senescent murine s-FA undergoes vascular remodelling associated with increases in stretch-activated contractility and sensitivity to NO/cGMP/PKG system. |
| تدمد: | 1742-7843 1742-7835 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eeb94a6f72c629ccb4c3673ede6a2a78Test https://doi.org/10.1111/bcpt.13675Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....eeb94a6f72c629ccb4c3673ede6a2a78 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17427843 17427835 |
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