Presentation description

M Judge, R Vieira, C Olmar, J Wilson, A Chaix, S Mookherjee, J D Symons

Department of Nutrition and Integrative Physiology, Molecular Medicine Program, University of Utah, Salt Lake City, UT

Eleven million Americans work night shifts/rotating schedules. This lifestyle choice disrupts circadian rhythm, increasing risk for pathologies such as heart disease, but impact on arterial function is unclear. To test this, 1-month old male mice consumed standard chow and water ad libitum and were maintained on a 12-hr dark (active) cycle from 0600-1800 and a 12-hr light (inactive) cycle from 1800-0600 for 4-months (Con, n=5). To disrupt circadian rhythm, we used a chronic jet lag model developed by Filipski et al. (American Journal of Cancer Research, 2004). Age-matched male littermates had their inactive cycle advanced by 8-hr, thus shortened to 4-hr, three times per week for 4-months (CJL, n=5). CJL reduces the expression of clock genes mPer2 and mRev-erb⍺, and clock protein mPER1 in the SNC, a neural network in the hypothalamus that regulates the circadian rhythm, verifying circadian disruption. At 5-months, segments of thoracic aorta were collected to: (i) complete stress vs. strain curves (myography); (ii) determine arterial diameter and intimal-medial thickness (histology), to calculate the elastic modulus. Mesenteric resistance arteries (MRAs) and middle cerebral arteries (MCAs) were acquired to assess vascular reactivity using isometric and isobaric myography, respectively. Neither intrinsic arterial stiffness nor MRA or MCA endothelium-dependent or- independent vasorelaxation were different between Con and CJL. To assess the impact of duration, a second cohort of Con (n=5) and CJL (n=5) were evaluated at 8-months. Results concerning arterial stiffness and vascular reactivity are being analyzed. Because >30% of the population is obese, which can independently heighten arterial stiffness and reduce arterial function, a third cohort of male mice maintained the Con (n=5) and CJL (n=8) protocols for 8-months while consuming a high-fat diet. Results are being analyzed.