Cholinergic and anticholinergic drug effects on survival during hypoxia: significant gender differences

We examined central and peripheral components of cholinergic drug protection against hypoxia in male and female mice. Survival times were measured in groups of control and treated (i.p. injection) animals exposed to hypoxia (5% O2/95% N2). Body temperatures were also measured in separate groups of normoxic control and treated animals. Control (NaCl) animals of both sexes survived only 3.5 and 3.7 min of hypoxia. After physostigmine (0.2 mg/kg), however, significantly more females (82.4%) than males (40.5%) survived 35 to 60 min of hypoxia, although physostigmine hypothermia was equal in both sexes. Pilocarpine (5 mg/kg) also produced a gender difference (female > male) in survival, despite equal hypothermia. Hypothermia after neostigmine (0.2 mg/kg) was equal in males and females, yet neither sex survived longer than controls. The protective and hypothermic effects of physostigmine were blocked by atropine sulphate (5 mg/kg). In contrast, atropine methylnitrate (2 mg/kg) did not block physostigmine hypothermia in either sex, but markedly decreased physostigmine's protective effect in females. Beside the significant gender differences in physostigmine and pilocarpine protection, the results show that hypothermia alone is not responsible for protection or for the gender difference. Survival prolongation in males appears to depend solely on physostigmine's central actions. In females, peripheral actions (e.g., hormone release from pituitary and ovary) may contribute to protection and to the gender difference.