Torpor state protects against cosmic radiation-induced vascular dysfunction in 13-lined ground squirrels

Introduction: Long-duration deep space missions expose humans to chronic low-dose galactic cosmic radiation (GCR). Radiation has been associated with vascular dysfunction, accelerated atherosclerosis, and increased risk of cardiovascular diseases. Hibernating mammals are known to be more tolerant of high dose gamma radiation than other species that do not hibernate (eg. rats) particularly during torpor. During torpor, hibernating ground squirrels undergo profound cardiovascular adaptations, such as significant decreases in heart rate, blood pressure, and blood flow. This highlights the plasticity of the vasculature under extreme physiological fluctuations. While hibernation has been proposed as an effective strategy for long-term space mission years ago, in part due to enhanced radioprotection, it is yet to be determined whether this extends to protection against radiation-induced vascular injury. This study investigated the effects of simulated GCR on vascular reactivity in isolated aorta from 13-lined ground squirrels in hibernation and active seasons. We hypothesized that squirrels that received simulated GCR during active season will exhibit vascular dysfunction and that exposure to GCR during hibernation will mitigate these adverse effects. Methods/Results: In this study, 13-lined ground squirrels were exposed to GCR delivered as low-dose chronic high-LET radiation (252Cf; 2.16 mgy/d). Animals were either exposed to GCR or housed in the same facility without GCR for 6 months during the hibernation or active season. Following exposure, vascular function was assessed in the thoracic aorta ex vivo using wire myography. No significant differences in vasoconstriction were detected between control and irradiated aorta in response to phenylephrine (PE) as measured by EC 50 concentration in either the hibernating (p = 0.9214) or active (p = 0.5564) squirrels. However, the irradiated active squirrels showed an increase in maximum vasoconstriction response to PE (10-5 M) compared to controls (p = 0.0747). While no differences were observed between irradiated hibernating squirrels and control. Interestingly, no differences in vasodilatory responses were observed as measured by EC50 concentration in response to acetylcholine (10-10-10-4 M). Conclusion: Previous literature demonstrates that radiation can induce vascular dysfunction, particularly in arterial relaxation. However, our study showed that the irradiated active squirrels did not have impaired vasodilatory response. Suggesting that this species may possess innate physiological resilience against radiation regardless of the state at which the squirrels receive radiation. However, we did observe an increased contractile response alluding to vascular dysfunction following irradiation during active season. Together our results provide evidence for protection of torpor state against radiation-induced vascular impairment. In addition to depression of metabolism, torpor state is also characterized by unique metabolic shift. We aim to further elucidate whether metabolic reprogramming in vasculature during torpor state confers the radioresistant ability. Identifying such protective mechanisms may provide insights for mitigating cardiovascular disease risk in future space travels. Funding; NASA grant #80NSSC24K0650, SR, HRP, NIAC This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.