Endothelial ATP-Sensitive Potassium Channel Protects Against the Development of Hypertension and Atherosclerosis
| Autor: | Andrew Tinker, Leona Ojake, Qadeer Aziz, Yiwen Li, Naomi Anderson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Blood Pressure chemistry.chemical_compound Mice 0302 clinical medicine KATP Channels Enos Endothelial dysfunction Enzyme Inhibitors Mesenteric arteries Mice Knockout biology Pinacidil ion channels Vasodilation medicine.anatomical_structure NG-Nitroarginine Methyl Ester Treatment Outcome ComputingMethodologies_DOCUMENTANDTEXTPROCESSING medicine.medical_specialty hypertension ATP-sensitive potassium channel Endothelium Nitric Oxide Synthase Type III Diet High-Fat 03 medical and health sciences Apolipoproteins E Internal medicine medicine.artery Internal Medicine medicine Animals Antihypertensive Agents Aorta business.industry Endothelial Cells Original Articles biology.organism_classification medicine.disease Atherosclerosis Peptide Fragments Mice Inbred C57BL 030104 developmental biology Blood pressure Endocrinology chemistry business 030217 neurology & neurosurgery |
| Zdroj: | Hypertension (Dallas, Tex. : 1979) |
| ISSN: | 1524-4563 0194-911X |
| Popis: | Supplemental Digital Content is available in the text. In the endothelium, ATP-sensitive potassium (KATP) channels are thought to couple cellular metabolism with membrane excitability, calcium entry, and endothelial mediator release. We hypothesized that endothelial KATP channels have a broad role protecting against high blood pressure and atherosclerosis. Endothelial-specific Kir6.1 KO mice (eKO) and eKO mice on an apolipoprotein E KO background were generated (A-eKO) to investigate the role of KATP channels in the endothelium. Basal blood pressure was not elevated in eKO mice. However, when challenged with a high-salt diet and the eNOS inhibitor L-NAME, eKO mice became more hypertensive than their littermate controls. In aorta, NO release at least partly contributes to the endothelium-dependent vasorelaxation induced by pinacidil. In A-eKO mice atherosclerotic plaque density was significantly greater than in their littermate controls when challenged with a high-fat diet, particularly in the aortic arch region. Levels of endothelial dysfunction markers were higher in eKO compared with WT mice; however, these were not significant for A-eKO mice compared with their littermate controls. Furthermore, decreased vascular reactivity was observed in the mesenteric arteries of A-eKO mice, but not in aorta when on a high-fat diet. Our data support a role for endothelial Kir6.1-containing KATP channels in the endothelial protection against environmental stressors: the maintenance of blood pressure homeostasis in response to high salt and endothelial integrity when challenged with a high-fat diet. |
| Databáze: | OpenAIRE |
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