Deletion of T-type calcium channels Cav3.1 or Cav3.2 attenuates endothelial dysfunction in aging mice
| Autor: | Kristina S. Lyngsø, Charlotte Brasch-Andersen, Kenneth Andersen, Anne D Thuesen, Pernille B. Lærkegaard Hansen, Paul M. Vanhoutte, Mark Burton |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Physiology Clinical Biochemistry Vasodilation 030204 cardiovascular system & hematology Nitric oxide Calcium Channels T-Type/genetics Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Enos Physiology (medical) Internal medicine medicine.artery Aorta/growth & development medicine Animals Endothelial dysfunction Mesenteric arteries Aorta Mesenteric Arteries/growth & development biology Chemistry T-type calcium channel medicine.disease biology.organism_classification Aging/metabolism Mice Inbred C57BL 030104 developmental biology Endocrinology medicine.anatomical_structure Vasoconstriction Nitric Oxide/metabolism Female medicine.symptom Gene Deletion Endothelium Vascular/metabolism |
| Zdroj: | Thuesen, A D, Andersen, K, Lyngsø, K S, Burton, M, Brasch-Andersen, C, Vanhoutte, P M & Hansen, P B L 2018, ' Deletion of T-type calcium channels Cav3.1 or Cav3.2 attenuates endothelial dysfunction in aging mice ', Pflügers Archiv-European Journal of Physiology, vol. 470, no. 2, pp. 355–365 . https://doi.org/10.1007/s00424-017-2068-x |
| ISSN: | 1432-2013 0031-6768 |
| DOI: | 10.1007/s00424-017-2068-x |
| Popis: | Impairment of endothelial function with aging is accompanied by reduced nitric oxide (NO) production. T-type Cav3.1 channels augment nitric oxide and co-localize with eNOS. Therefore, the hypothesis was that T-type channels contribute to the endothelial dysfunction of aging. Endothelial function was determined in mesenteric arteries (perfusion) and aortae (isometric contraction) of young and old wild-type (WT), Cav3.1, and Cav3.2 knockout mice. NO production was measured by fluorescence imaging in mesenteric arteries. With age, endothelium-dependent subsequent dilatation (following depolarization with KCl) of mesenteric arteries was diminished in the arteries of WT mice, unchanged in Cav3.2(-/-) preparations but increased in those of Cav3.1(-/-) mice. NO synthase inhibition abolished the subsequent dilatation in mesenteric arteries and acetylcholine-induced relaxations in aortae. NO levels were significantly reduced in mesenteric arteries of old compared to young WT mice. In Cav3.1(-/-) and Cav3.2(-/-) preparations, NO levels increased significantly with age. Relaxations to acetylcholine were significantly smaller in the aortae of old compared to young WT mice, while such responses were comparable in preparations of young and old Cav3.1(-/-) and Cav3.2(-/-) mice. The expression of Cav3.1 was significantly reduced in aortae from aged compared to young WT mice. The level of phosphorylated eNOS was significantly increased in aortae from aged Cav3.1(-/-) mice. In conclusion, T-type calcium channel-deficient mice develop less age-dependent endothelial dysfunction. Changes in NO levels are involved in this phenomenon in WT and Cav3.1(-/-) mice. These findings suggest that T-type channels play an important role in age-induced endothelial dysfunction. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink