Resveratrol mitigates hypercholesterolemia exacerbated hyperthermia in chronically heat-stressed rats

Hypercholesterolemia (HC) is the major leading cause of cardiovascular disease worldwide. Such atherogenic aberration deeply impacts blood circulation. Resveratrol (R) is a polyphenol that has received attention as a hypolipidemic, antioxidant, and vascular agility advocate. Efficient blood redistribution is a key element in mammalian thermoregulation. We hypothesized that R treatment may aid in mitigating hyperthermic responses under both acute and chronic heat stress (HS) conditions in HC male rats.

All rats were initially fitted with miniaturized thermologgers to measure core body temperature (T_core). With a 2 × 2 factorial arrangement, four groups were randomly allotted, in which half of the animals ingested an HC diet (C+), while the other half ingested a control (C-) diet, throughout the whole study duration of 35 days. Seven rats from each dietary treatment, however, received R (R+; 13 mg/kg BW/day), while the rest received normal saline (R-) for 5 continuous days. All animals were maintained at thermoneutrality (TN; ambient temperature; T_a=23.15±0.04°C) for a period of 30 continuous days (days 0-29). On day 29, an acute HS (HS; T_a=35.86±0.37°C; for 9 nocturnal h) was imposed. Then, from day 29, a chronic HS protocol (T_a=32.28±1.00°C) was maintained until the past day of the trial (day 34), after which blood samples were drawn for analyses of platelet (PL) count, total antioxidant activity (TAO), total cholesterol (TC), triglycerides (TGs), and lipid peroxidation (LP).

Switching animals from TN to HS resulted in abrupt rises in T_core. The HC diet induced a significant (p<0.01) hyperlipidemia over the control of diet-consuming rats. Interestingly, the hyperthermic response to acute HS was highly pronounced in the rats consuming the C- diet, while the C+ diet exacerbated the chronic HS-induced hyperthermia. Despite failure to improve TAO in the C+ diet, R+ treatment caused a marked (p<0.05) decline in nighttime - hyperthermia in C+ rats, likely by enhancing blood flow to extremities (for heat dissipation) as delineated by drastic downregulations of C+ related rises in PL, TC, TG, and LP (HC diet by R+ interaction; p<0.03).

The hyperthermic response in C- groups was attributed to higher amount of feed intake than those consuming the C+ diet. Yet, the R+ improvement of thermoregulation in the C+ group was likely related to enhancement of vascular hemodynamics. Resveratrol intake mitigated chronic HS-evoked hyperthermia in rats. Such an approach is worthy to follow-up in other mammals and humans.