Interindividual variation in acclimatization to altitude suggests a genetic component, and several candidate genes have been proposed. One such candidate is a polymorphism in the angiotensin converting enzyme (ACE) gene, where the insertion (I-allele), rather than the deletion (D-allele), of a 287 base pair sequence has been associated with lower circulating and tissue ACE activity and has a greater than normal frequency among elite endurance athletes and, in a single study, among elite high altitude mountaineers. We tested the hypothesis that the I-allele is associated with successful ascent to the extreme high altitude of 8000 m. 141 mountaineers who had participated in expeditions attempting to climb an 8000-m peak completed a questionnaire and provided a buccal swab for ACE I/D genotyping. ACE genotype was determined in 139 mountaineers. ACE genotype distribution differed significantly between those who had successfully climbed beyond 8000 m and those who had not (p = 0.003), with a relative overrepresentation of the I-allele among the successful group (0.55 vs. 0.36 in successful vs. unsuccessful, respectively). The I-allele was associated with increased maximum altitudes achieved: 8079 +/- 947 m for DDs, 8107 +/- 653 m for IDs, and 8559 +/- 565 m for IIs (p = 0.007). There was no statistical difference in ACE genotype frequency between those who climbed to over 8000 m using supplementary oxygen and those who did not (p = 0.267). This study demonstrates an association between the ACE I-allele and successful ascent to over 8000 m.
The effect of chlorpromazine on the overt emotional activity of a hybrid strain of rats has been measured using an altered "emotionality rating scale." It has been found that 8 mg/kg of chlorpromazine intraperitoneally reduced the activity of rats with the septal nuclei destroyed, normal rats and control rats to the same emotional rating. This effect has been related to the postulated interrelationship of the septal area and the amygdaloid complex of nuclei. It seemed that impulses traversing the septal nuclei might be re-routed, so that destruction of the septal area need not necessarily cause total abolition of " septal-function."It has been suggested by Olds & Travis (1960) that chlorpromazine can inhibit a forebrain system, while leaving intact the functions of a midbrain system. This is compatible with the hypothesis that chlorpromazine activity is localized within the limbic lobe.A marked increase in emotional behaviour of animals after experimental ablation of the septal region of the forebrain has been reported (Brady & Nauta, 1953;King, 1958 ;King & Meyer, 1958). This hyper-emotionality is manifested by violent attack or flight reactions in response to previously neutral or innocuous stimuli. There is extreme muscular tension to a degree rarely, if ever, noted in the normal animal. Therefore, it is possible that the septal nuclei exert an important function in the "physiological tranquillization" of rats. Destruction of the septal nuclei results in the excited animal because the septum normally counterbalances a stimulatory area.Chlorpromazine has been shown to cause an activity shift in the opposite direction to that produced by septal destruction (Hunt, 1957). This author showed that, following chlorpromazine administration, both septal operated and unoperated rats were depressed.A study of the activity of chlorpromazine in rats with surgically destroyed septal nuclei has been made with a view to testing the hypothesis that the septal area "counterbalances " a stimulatory area of the brain. To locate the site of actions of chlorpromazine the extent of the effect of the drug on animals which were septally hyperactive was observed, and compared with the effect of chlorpromazine on normal rats and on control animals which had had a " sham " operation.
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