Extended breath-hold (
apnea) bouts are routine during diving and sleeping in seals. These
apneas result in
oxygen store depletion and blood flow redistribution towards obligatory
oxygen-dependent tissues, exposing seals to critical levels of
ischemia and
hypoxemia. The subsequent reperfusion/reoxygenation has the potential to increase
oxidant production and thus oxidative stress. The contributions of extended
apnea to oxidative stress in adapted mammals are not well defined. To address the hypothesis that
apnea in seals is not associated with increased oxidative damage, blood samples were collected from northern elephant seal pups (N=6) during eupnea, rest- and voluntary submersion-associated
apneas, and post-
apnea (recovery). Plasma
4-hydroxynonenal (HNE), 8-isoprostanes (8-isoPGF(2α)),
nitrotyrosine (NT),
protein carbonyls,
xanthine and
hypoxanthine (HX) levels, along with
xanthine oxidase (XO) activity, were measured.
Protein content of XO,
superoxide dismutase 1 (Cu,ZnSOD),
catalase and
myoglobin (Mb), as well as the nuclear content of
hypoxia inducible factor 1α (HIF-1α) and
NF-E2-related factor 2 (Nrf2), were measured in muscle biopsies collected before and after the breath-hold trials. HNE, 8-iso
PGF(2α), NT and
protein carbonyl levels did not change among eupnea,
apnea or recovery. XO activity and HX and
xanthine concentrations were increased at the end of the
apneas and during recovery.
Muscle protein content of XO, CuZnSOD,
catalase, Mb, HIF-1α and Nrf2 increased 25-70% after
apnea. Results suggest that rather than inducing the damaging effects of
hypoxemia and
ischemia/reperfusion that have been reported in non-diving mammals,
apnea in seals stimulates the oxidative stress and hypoxic hormetic responses, allowing these mammals to cope with the potentially detrimental effects associated with this condition.