TRPV1 modifies cardiovascular and autonomic responses to extreme heat in a housing-specific manner
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Extreme heat events are classified as the leading cause of weather-related death in the United States and are associated with increased cardiovascular morbidity and mortality, both in acute and chronic conditions. Further, it is known that these adverse effects do not occur proportionately across populations, indicating that living conditions might have an effect on the physiological and adaptive responses to heat stress. The synergistic effects of housing (i.e. psychosocial stress) and extreme heat remain understudied, and the role of transient receptor potential vanilloid 1 (TRPV1) in modulating these responses represents a novel mechanistic evaluation of these non-chemical stressors. Female C57BL6/J mice surgically implanted with biopotential radiotelemeters that measured continuous heart rate (HR), core body temperature (Tco), activity, and electrocardiograms (ECG) were randomly separated into either enriched (EH) or depleted housing (DH) for 4 weeks. Mice then underwent a single intraperitoneal injection of either a vehicle-control or a TRPV1 antagonist (BCTC) 30-min before an exposure to a 1-hr normal temperature (22°C) control (NT), followed by three consecutive days of 1-hr extreme heat exposures (~36°C). Before exposures, mice in DH had a higher resting HR, lower Tco and activity levels, and shorter RR-interval and QRS complex on the ECG. The TRPV1 antagonist prevented an increase in HR in DH-mice during the NT-control sham, however the DH-BCTC mice had significantly higher HR and RR-intervals during the first and third day of EHE. BCTC also induced a decrease in heart-rate variability (HRV) throughout the NT-control and the first and second day of EHE, followed by a significant increase in HRV on the third day of EHE. Further, TRPV1 antagonism resulted in significant and sustained elevations in Tco and activity during and after heat exposures, that persisted up to 1-wk post-exposure. Overall, our results portray a complex relationship between housing conditions, extreme heat, and the role of TRPV1 in cardiovascular response. In addition, radiotelemetry revealed signs of increased autonomic and thermoregulatory perturbations when TRPV1 was blocked in DH mice, which was not present with EH. Our findings show that TRPV1 plays a role in the response to extreme heat in a housing-specific manner, and further work is needed to characterize whether the changes are related to epigenetic, gene expression, immunological, or other mechanisms that might confer vulnerability to heat stress.