Endothelial ATP-Sensitive Potassium Channel Protects Against the Development of Hypertension and Atherosclerosis

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 76; no. 3; pp. 776 - 784
• Main Authors: Li, Yiwen, Aziz, Qadeer, Anderson, Naomi, Ojake, Leona, Tinker, Andrew
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01.09.2020; Lippincott Williams & Wilkins
• Subjects: Animals; Antihypertensive Agents - pharmacology; Apolipoproteins E - metabolism; Atherosclerosis - metabolism; Atherosclerosis - prevention & control; Blood Pressure - drug effects; Blood Pressure - physiology; Diet, High-Fat - adverse effects; Endothelial Cells - drug effects; Endothelial Cells - physiology; Enzyme Inhibitors - pharmacology; Hypertension - drug therapy; Hypertension - metabolism; KATP Channels - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide Synthase Type III - antagonists & inhibitors; Nitric Oxide Synthase Type III - metabolism; Original; Peptide Fragments - metabolism; Pinacidil - pharmacology; Treatment Outcome; Vasodilation - drug effects; Vasodilation - physiology; atherosclerosis; endothelium; hypertension; ion channels
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.120.15355

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 stressorsthe maintenance of blood pressure homeostasis in response to high salt and endothelial integrity when challenged with a high-fat diet.