Primary hypoxic tolerance and chemical preconditioning during estrus cyclein mice

Background and Purpose-Exogenous application of estrogens or progesterone a meliorates hypoxic/ischemic cell damage. This study investigates whether va lues of primary and induced hypoxic tolerance vary endogenously during the estrus cycle in female mice. Methods-Population spike amplitude (PSA) and NADH were measured during hypo xic hypoxia and recovery in hippocampal slices from untreated control anima ls (C slices) and slices prepared from animals pretreated in vivo with a si ngle intraperitoneal injection of 3-nitropropionate (3NP) (3NP slices) or a cetylsalicylate (ASA) (ASA slices). Results-Posthypoxic recovery of PSA was dose dependent in 3NP slices from m ales, with maximal recovery on pretreatment attained with 20 mg/kg 3NP (82/-32% [mean+/-SD]; C slices, 38+/-29%; P<0.01). PSA recovered to 17+/-12% i n C slices during proestrus, 43+/-23% during estrus, and 63+/-44% during di estrus, In 3NP slices, recovery of PSA increased to 57+/-36% (P<0.05) durin g proestrus. Hypoxic tolerance was not increased in other stages of the est rus cycle. Hypoxic NADH increase during proestrus declined from 212+/-76% i n C slices to 133+/-11% in 3NP slices (P<0.05). Recovery of PSA in ASA slic es was 75+/-36% (P<0.01 versus control) in males and 48+/-34% during proest rus (P<0.05 versus ASA slices from males). Conclusion-Primary and induced hypoxic tolerance are endogenously modulated during the estrus cycle. Differences in hypoxic oxidative energy metabolis m mediate part of the differential tolerance. Experimental and clinical the rapeutic strategies against cerebral ischemia/hypoxia need to consider sex- related dependence.