1. The effect of 5 consecutive days of hill walking on electrolyte balance, fluid homeostasis, plasma renin activity and plasma aldosterone concentration was studied in five male subjects. 2. The 5-day exercise period was preceded by a 4-day control period and followed by a 4-day recovery period. Throughout the 13-day study subjects ate a fixed diet. 3. After 5 days of exercise subjects had retained a mean of 264 mmol (SD 85) of sodium. Plasma sodium concentration remained constant at 142.0 mmol/l (SD 5.4). This indicates an expansion of the extracellular space by 1.84 litres. 4. By the end of the exercise period there was a positive water balance of about 0.9 litre. Thus there was a net movement of 0.94 litre of fluid from the intracellular to the extracellular space. 5. Packed cell volume decreased from a mean of 43.5% to 37.9% after 5 days of exercise, indicating that about 0.9 litre of the extracellular fluid entered the vascular compartment. The remaining fluid may be responsible for the significant increase in lower leg volume. 6. During the exercise period plasma aldosterone concentration and plasma renin activity rose, and there was a highly significant correlation between these values and the sodium retention. There was also a significant correlation between sodium retention and the increase in leg volume, which suggests that oedema may be the result of prolonged exercise of this type.

The effect of increasing end-tidal enflurane concentration on the auditory evoked response was studied in six patients. After a standard induction, anesthesia was maintained with 70% nitrous oxide in oxygen and the end-tidal enflurane concentration was increased gradually from 0 to 1% over a period of 30 min. The averaged auditory evoked response was derived from the electroencephalogram and measurements were made of the latencies and amplitudes of waves I, III, V, Pa and Nb within the auditory evoked response. The latencies of all waves and the interpeak latencies I to V and III to V showed significant linear increases and the amplitudes of Pa and Nb showed significant linear decreases with increasing end-tidal enflurane concentration. These results could not be explained by changes in deep body temperature or end-tidal carbon dioxide concentration. The study demonstrated a dose-related direct effect of enflurane on the brainstem and early cortical components of the auditory evoked response.

The possibility that hypoxia might inhibit the secretion of angiotension-converting enzyme (ACE) would explain the low concentrations of aldosterone reported in humans at high altitude. To observe the effect of such a reduction in ACE concentration on the plasma aldosterone concentration (PAC) four subjects performed mild exercise throughout a 2-h study so as to elevate their plasma renin activity (PRA). After the first 60 min breathing air they were switched to breathing 12.8% O2 (4,000 an altitude equivalent). Venous samples were taken at intervals for hormone analysis. Results showed the expected rise of PRA and PAC both tending toward a plateau after about 45 min. There was no significant change in ACE activity (F = 0.065). Hypoxia produced a further 50% rise in PRA but a fall in PAC and a 30% reduction in ACE activity. Angiotensin I concentrations closely followed PRA throughout (r = 0.984). These results indicate that during exercise acute hypoxia changes the usual close relationship between PAC and PRA by reducing ACE activity.

SUMMARY1. The effects of intravenous morphine, (-)-naloxone and (+ )-naloxone have been studied on three ipsilateral cutaneo-muscular reflexes in spinal rabbits.2. Morphine, 3 mg/kg caused a slow-onset depression of all three reflexes. This effect was naloxone reversible.3. The ipsilateral extensor reflexes, sural to gastrocnemius medialis and saphenous to vastus lateralis were both enhanced to more than double control size following a 5 sag/kg dose of naloxone given in the absence of morphine. For the suralgastrocnemius reflex, naloxone potentiated the reflex drive from all groups of myelinated afferent fibres.4. The ipsilateral flexion reflex, sural to semitendinosus, was only weakly enhanced by naloxone, the 5 ,ug dose leading to an increase in the size of the reflex to 130 % of control. 5. All observed actions of naloxone were stereospecific as the enantiomer (+ )-naloxone failed to affect any of the reflexes even in a dose of 50 ltg/kg.6. We conclude from these findings that opioid peptides are tonically released in rabbit spinal cord, and that they have differential effects in control of flexion and extension reflexes. It is suggested that the ipsilateral extension reflexes are held under a more powerful opioid-mediated depression than that operating upon the flexion reflexes, and that this difference may be related to the greater inhibitory inflow to extensor motoneurones from ipsilateral skin areas.

The effect of 7 wk altitude exposure on plasma renin activity (PRA), plasma aldosterone concentration (PAC), and angiotensin-converting enzyme (ACE) activity was studied in 10 male subjects at 4,500 m. There was an initial increase in PRA and a reduction in PAC and ACE. The reduction in ACE was significantly greater in the four subjects who had frequently been exposed to extreme altitudes than in the other six subjects. These changes had returned to control values between 12 and 20 days. Exercise caused a marked elevation of PRA and PAC, but the PAC response to PRA was blunted compared with that at sea level. The ratio PAC/PRA at rest was reduced initially but returned to control values with a similar time course to that of ACE activity. The results are compatible with the hypothesis that ACE activity governs the adrenal response to PRA.

The combined effect of exercise and altitude on the renin-aldosterone system was studied in six male subjects on a fixed diet. After 4 control days at rest and at low altitude, subjects ascended to 3,100 m and took about 7 h exercise daily for 5 days. There followed a 4-day recovery period at low altitude. Daily blood samples were taken for estimation of plasma renin activity (PRA), plasma aldosterone concentration (PAC), and angiotensin converting-enzyme (ACE) activity. Results showed a maximal rise in PRA and PAC with exercise at altitude maximal on the first 2 days. ACE activity fell by 23% at altitude. Compared with similar exercise at sea level, the rise in PAC was comparable but the rise in PRA was four times greater, indicating a marked decrease in PAC response to PRA. It is suggested that this loss of sensitivity of PAC to PRA is mediated by the measured reduction in ACE activity.

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