Kimberly Stratford1, Najwa Haykal-Coates2, Leslie Thompson3, Aimen Farraj3, Mehdi Hazari4. 1. Curriculum in Toxicology and Environmental Medicine, University of North Carolina - Chapel Hill, Chapel Hill, NC, 27599, United States. 2. Inhalation Toxicology Facilities Branch, Public Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, United States. 3. Cardiopulmonary and Immunotoxicology Branch, Public Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, United States. 4. Cardiopulmonary and Immunotoxicology Branch, Public Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, United States. Electronic address: hazari.mehdi@epa.gov.
Abstract
BACKGROUND: Studies indicate that chronic vitamin D deficiency (VDD) may predispose to hypertension, yet, there is very little data characterizing its direct cardiac effects. Vitamin D modulates the function of transient receptor potential C cation channels (TRPC), which is a mechanosensitive cation channel that plays a role in cardiac slow-force responses to hemodynamic changes. The purpose of this study was to determine the cardiac effects of VDD and the potential role of TRPC. METHODS: Three-week old mice were placed on a VDD or normal diet (ND) for 19 weeks. Mice were then implanted with radiotelemeters for the measurement of heart rate (HR) and heart rate variability (HRV), while a separate group was anesthetized to measure blood pressure (BP) and left ventricular function using an intraventricular probe. Animals were treated with a TRPC antagonist or vehicle after which they were challenged with dobutamine to measure cardiac responses. RESULTS: VDD mice had significantly increased BP (72 ± 3 mmHg vs. 62 ± 2 mmHg) and left ventricular pressure (LVP) (84.6 ± 0.8 mmHg vs. 78.2 ± 2.0 mmHg), and decreased cardiac contractility (-3 % vs. + 11 %) and HR response (+8 % vs. + 13 %) to dobutamine when compared to ND. These responses were blocked by the TRPC antagonist. HRV decreased with increasing dobutamine doses in ND but not VDD mice, however, the antagonist had no effect. CONCLUSION: VDD increases BP and alters cardiac mechanical function in mice, the latter appears to be mediated by TRPC, in particular TRPC6. Although the cardiac effects might be due to increased BP, it is likely that VDD also affects the function of the heart directly. This is the first study to demonstrate the potentially deleterious effects of VDD on cardiac function and the role of TRPC6 in this response. Published by Elsevier Ltd.
BACKGROUND: Studies indicate that chronic vitamin D deficiency (VDD) may predispose to hypertension, yet, there is very little data characterizing its direct cardiac effects. Vitamin D modulates the function of transient receptor potential C cation channels (TRPC), which is a mechanosensitive cation channel that plays a role in cardiac slow-force responses to hemodynamic changes. The purpose of this study was to determine the cardiac effects of VDD and the potential role of TRPC. METHODS: Three-week old mice were placed on a VDD or normal diet (ND) for 19 weeks. Mice were then implanted with radiotelemeters for the measurement of heart rate (HR) and heart rate variability (HRV), while a separate group was anesthetized to measure blood pressure (BP) and left ventricular function using an intraventricular probe. Animals were treated with a TRPC antagonist or vehicle after which they were challenged with dobutamine to measure cardiac responses. RESULTS: VDD mice had significantly increased BP (72 ± 3 mmHg vs. 62 ± 2 mmHg) and left ventricular pressure (LVP) (84.6 ± 0.8 mmHg vs. 78.2 ± 2.0 mmHg), and decreased cardiac contractility (-3 % vs. + 11 %) and HR response (+8 % vs. + 13 %) to dobutamine when compared to ND. These responses were blocked by the TRPC antagonist. HRV decreased with increasing dobutamine doses in ND but not VDD mice, however, the antagonist had no effect. CONCLUSION: VDD increases BP and alters cardiac mechanical function in mice, the latter appears to be mediated by TRPC, in particular TRPC6. Although the cardiac effects might be due to increased BP, it is likely that VDD also affects the function of the heart directly. This is the first study to demonstrate the potentially deleterious effects of VDD on cardiac function and the role of TRPC6 in this response. Published by Elsevier Ltd.
Entities:
Keywords:
Cardiovascular; Hypertension; TRPC; Vitamin D deficiency
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