BK channel β‐1 subunit deficiency exaggerates vascular fibrosis and organ damage in high fat diet‐induced obesity in mice (857.10)

BK channels regulate arterial tone. Studies done in humans and animals suggest that impaired BK channel function contributes to obesity associated hypertension due to higher myogenic tone and increased norepinephrine (NE) reactivity. In current study, we continually measured mean arterial pressure (MAP) and heart rate (HR) using radiotelemetry in high fat (HF) diet fed wild type (WT) and BK channel β1‐subunit knockout (BK β1‐KO) mice during last 11 weeks of HF‐fed. After 24 weeks on HF‐fed, body weight and blood glucose levels were similar in all mice. All mice were normotensive, but BK β1‐KO mice showed a progressive fall in HR when compared to WT mice. Atenolol (oral) or hexamethonium (ip) treatment reduced MAP and HR similarly in all mice, prazosin (oral) decreased MAP and increased HR in BK β1‐KO only. Mesenteric arteries (MA) from BK β1‐KO mice exhibited increased sensitivity to NE and BayK 8644, higher myogenic tone, increased wall thickness and smaller wall/lumen ratio compared to WT mice. BK β1‐KO mice also exhibited left ventricular hypertrophy, lower hematocrits and higher plasma creatinine levels than WT mice. Histological studies revealed more extensive collagen deposition in MA, coronary and renal arteries, myocardium and kidneys of BK β1‐KO compared to WT mice. Our results indicate that BK channel deficiency does not cause hypertension, but does promote vascular fibrosis and organ damage in HF‐fed mice. Grant Funding Source : Supported by NIH and AHA