Arginase inhibition and low‐dose sodium nitroprusside administration do not influence heat loss responses during exercise in aged humans
Authors: Meade Robert D , Fujii Naoto , Alexander Lacy M , Louie Jeffrey C , Boulay Pierre , Sigal Ronald J , Kenny Glen P 
Published: November 2023

Age‐related increases in arginase activity may contribute to the diminished cutaneous vasodilatory and sweating responses observed in older relative to younger adults, likely through pathways related to nitric oxide (NO). However, it remains to be elucidated whether arginase inhibition to functionally increase bioavailable NO modulates these heat loss responses in older adults exercising in the heat. Furthermore, it is unknown if the sensitivity of the cutaneous vasculature and sweat gland to NO is altered in older relative to young adults. Thus, the purpose of this study was to assess the influence of arginase inhibition and low‐dose sodium nitroprusside (SNP; an NO donor) administration on local cutaneous vascular conductance (CVC) and sweat rate (SR) in young and older adults during exercise in the heat. Ten young (23 ± 3 years) and nine older (66 ± 6 years) males had four intradermal microdialysis fibres inserted into the dorsal forearm skin that were continuously perfused with either: 1) lactated Ringer's (Control); 2) 10 mM NG‐nitro‐L‐arginine methyl ester (L‐NAME), a non‐selective NO synthase (NOS) inhibitor; 3) 5 mM Nω‐hydroxy‐nor‐Arginine + 5 mM S‐(2‐boronoethyl)‐L‐cysteine to inhibit arginase activity (Nor‐NOHA+BEC); 4) or 1 μM SNP. Participants performed two 30‐min bouts of semi‐recumbent cycling in the heat (35˚C) at a fixed rate of metabolic heat production of 400 W. The first (Ex1) and second (Ex2) exercise bouts were followed by 20‐ and 40‐min recovery periods, respectively. CVC and SR were continuously measured at each skin site. Relative to Control (Ex1, 57 ± 5; Ex2, 64 ± 8%CVC‐max), CVC was reduced with NOS inhibition (Ex1, 32 ± 10; Ex2, 33 ± 7%CVC‐max; both P<0.01) in the young adults and was not altered with arginase inhibition (Ex1, 60 ± 10; Ex2, 63 ± 10%CVC‐max; both P≥0.65) or the exogenous NO donor (Ex1, 63 ± 13; Ex2, 64 ± 12%CVC‐max; both P≥0.38). In the older adults, CVC was attenuated relative to Control (Ex 1, 69 ± 7; Ex2, 67 ± 7%CVC‐max) with NOS inhibition during the first (50 ± 16%CVCmax; P=0.02) but not second (50 ± 18%CVCmax; P=0.16) exercise bout. No differences in CVC were found between Control and the arginase inhibited (Ex 1, 68 ± 11%; Ex2, 68 ± 9%CVC‐max; both P≥0.78) and the NO donor (Ex 1, 58 ± 10; Ex2, 62 ± 9%CVC‐max; both P≥0.10) sites. Relative to Control (Ex1, 0.88 ± 0.20; Ex2 0.93 ± 0.18 mg·min−1·cm−2), SR was reduced with NOS inhibition (Ex1, 0.77 ± 0.18; Ex2, 0.80 ± 0.16 mg·min−1·cm−2; both P≤0.03) but unaltered with arginase inhibition (Ex1, 0.90 ± 0.20; Ex2, 0.92 ± 0.17 mg·min−1·cm−2; both P≥0.56) and the exogenous NO donor (Ex1, 0.83 ± 0.16; Ex2, 0.90 ± 0.21 mg·min−1·cm−2; both P≥0.18) in the young adults during both exercise bouts. In contrast, no differences between Control (Ex1, 0.98 ± 0.19; Ex2, 0.96 ± 0.19 mg·min−1·cm−2) and any treatment site were observed in the older adults (all P≥0.12). Our findings suggest that neither local arginase inhibition nor low‐dose administration of SNP modulate the heat loss responses in young or older adults during exercise in the heat.Support or Funding InformationNatural Sciences and Engineering Research Council of Canada (funding held by Glen P. Kenny)