Physiological Responses to Intermittent Environmental Heat Stress in Mice

Abstract

Environmental heat stress is an emerging ecological problem, yet the physiological mechanisms linking repeated heat exposure to cardiovascular disease risk remain incompletely understood. Here, we investigated the systemic, cardiovascular, metabolic, and immune consequences of intermittent environmental heat stress. C57BL/6J Mice were exposed to intermittent hyperthermia (30°C–37°C, 3 h/day, 4 days/week) for up to four weeks under controlled environmental conditions. The core body temperature, blood pressure, and endothelial activation were measured by SoHo telemetry devices, tail‐cuff, and intravital microscopy, respectively. During heat exposure (> 33°C) there was a level dependent increase in core body temperature and water and food intake exposures. Exposure to 37°C elicited a robust neuroendocrine stress response characterized by a 2–4‐fold increase in plasma corticosterone levels, > 50% reductions in plasma epinephrine, and a robust induction of heat shock proteins in the vasculature. Heat exposure also transiently reduced systolic and diastolic blood pressure by ~10 mmHg and > 30% depletion in circulating immune cell populations. Despite this systemic leukopenia, repeated heat stress (37°C, 3 h/day, 4 days/week, 4‐weeks) increased leukocyte rolling and adhesion to the vascular endothelium (> 3‐fold), indicative of enhanced endothelial activation. In contrast, repeated heat exposure had minimal effects on cardiac systolic function, arterial stiffness, plasma lipid levels, or markers of overt organ injury. These findings demonstrate that repeated environmental heat stress induces coordinated neuroendocrine, vascular, immune, and metabolic adaptations characterized by activation of heat shock pathways, immune remodeling, and endothelial activation that precede cardiovascular dysfunction.