Reperfusion that follows a period of ischaemia paradoxically reduces vasodilator function in humans and contributes to the tissue damage associated with an ischaemic event. Acute wholebody hot water immersion protects against vascular ischaemia-reperfusion (I-R) injury in young healthy humans. However, the effect of acute lower leg heating on I-R injury is unclear. Therefore, wileyonlinelibrary.com/journal/eph Experimental Physiology. 2020;105:302-311.

There is a sustained reduction in arterial blood pressure that occurs in aged adults following exposure to acute leg heating. However, the neurovascular mechanisms mediating this response remain unknown. Our findings demonstrate for the first time that this reduction in arterial blood pressure is mediated, in part, by a sympathoinhibitory effect that alters the compensatory neural response to hypotension in aged adults.

There is a sustained reduction in arterial blood pressure that occurs in aged adults following exposure to acute leg heating. However, the neurovascular and humoral mechanisms mediating this hypotensive response remain unknown. The purpose of this study was to test the hypothesis that circulating concentrations of the potent vasoconstrictor substance endothelin‐1 would be attenuated concurrently with arterial blood pressure in aged adults following exposure to acute leg heating. Thirteen young adults (6 female; age 25 ± 4; height 172 ± 9 cm; weight 74 ± 15 kg; mean ± SD) and 10 aged adults (6 female; age 69 ± 5; height 166 ± 4 cm; weight 71 ± 11 kg; mean ± SD) were exposed to 45 minutes of acute leg heating. Subjects wore a tube‐lined water‐circulating garment that allowed leg skin temperature to be clamped at ~40°C during heating. Intestinal temperature was measured throughout via a telemetric pill. Systemic vascular conductance was calculated as cardiac output divided by mean arterial pressure and measured prior to heating (pre‐heat) and 30 min after (recovery). Plasma endothelin‐1 concentrations were quantified at pre‐heat and recovery time points via an enzyme‐linked immunosorbent assay. Leg heating increased body core temperature in young adults by 0.4 ± 0.1 °C and by 0.8 ± 0.2 °C in aged adults (both P < 0.05 vs. 0 change). Body core temperature remained modestly elevated for both groups in recovery (both P < 0.05 vs. pre‐heat). Mean arterial blood pressure was well maintained in young adults following leg heating (pre‐heat, 86 ± 6 mmHg vs. recovery, 88 ± 7 mmHg; P = 0.4), but was markedly reduced in aged adults (pre‐heat, 101 ± 7 mmHg vs. recovery, 94 ± 6 mmHg; P < 0.05). Systemic vascular conductance in young adults did not differ from pre‐heat (69 ± 3 ml min−1 mmHg−1) to recovery (70 ± 3 ml min−1 mmHg−1; P = 0.7), whereas conductance was increased in aged adults (pre‐heat, 55 ± 6 ml min−1 mmHg−1 vs. recovery, 62 ± 5 ml min−1 mmHg−1; P = 0.07). Plasma endothelin‐1 concentrations did not differ between groups at the pre‐heat time point (young adults, 1.13 ± 0.13 pg ml−1 vs. aged adults, 1.44 ± 0.11 pg ml−1; P = 0.4). Plasma endothelin‐1 increased in recovery by 0.23 ± 0.42 pg ml−1 for young adults and by 0.20 ± 0.43 pg ml−1 for aged adults (both P < 0.05 vs. 0 change). These data suggest that increased circulating endothelin‐1 may contribute to the maintenance of arterial blood pressure in young adults following exposure to acute leg heating by limiting systemic vascular conductance. Despite an increase in plasma endothelin‐1 in aged adults, arterial blood pressure was reduced in parallel with an increase in systemic vascular conductance which suggests that endothelin‐1‐mediated vasoconstriction may be altered following leg heating. Alternatively, increased endothelin‐1 may be preventing a further deleterious reduction in arterial blood pressure in aged adults by restraining the increase in systemic vascular conductance. Support or Funding Information National Institutes of Health (R01AG059314) and laborat...