Life has evolved on a planet with rotation around itself and the Sun. A fundamental mechanism of adaptation is the capacity of time-keeping, such that daily and seasonal events can be anticipated and prepared for. Many physiological variables have a circadian pattern, which in mammals is controlled by a biological clock with its own period of 24 h, placed in the suprachiasmatic nucleus of the hypothalamus. Among the most studied are the patterns of activity (Act), body temperature (Tb) and metabolic rate (oxygen consumption, VO2, and carbon dioxide production, VCO2). In the rat, a mostly nocturnal animal, all these variables increase during the dark hours of the night. Since all of them are known to influence pulmonary ventilation (VE), it is expected that also the breathing pattern, and possibly its controlling mechanisms, will present circadian oscillations. In rats chronically instrumented for measurements of Tb and Act by telemetry, VO2 and VCO2 were measured continuously for several days by an open-circuit method, while VE was monitored by a modification of the barometric technique . All variables of the breathing pattern (tidal volume VT, frequency f, and VE) increased in the dark (D) compared to the light (L) hours, with minor L-D differences in VE/VO2. The L-D differences in VE, and in all other parameters, persisted when comparisons between the L-D phases were made for the same level of either very low or very high Act, indicating that the oscillations in breathing pattern do not depend on Act. Indeed, ongoing experiments on rats in which circadian patterns are disturbed by sudden phase shifts between D and L, indicate a very poor correlation between levels of Act and breathing, which is much better correlated with Tb.
Sustained hypoxia (10% O2) blunted the amplitude of the circadian oscillations of all variables, Act being the least affected, and Tb the most [2,3]. In constant L ('free running' conditions), in which the natural period of the clock is unmasked, the effects of hypoxia on the Tb oscillations were not accompanied by a change in the clock period , and were not abolished by sino-aortic denervation , suggesting that hypoxia does not affect the clock itself but acts elsewhere centrally to affect the circadian patterns, possibly at the level of the hypothalamic thermoregulatory centers. Alterations in Tb patterns were also observed in men living intermittently at high altitude . Preliminary observations in adult rats seem to indicate that the hypoxic effects on the oscillations of Tb are less marked in females than males.
Sustained hypercapnia had minimal effects on Tb, activity, VO2 and VCO2, and, as observed during sustained hypoxia , the degree of hyperventilation (percent increase in VE/VO2) was essentially independent of the time of the day.
In conclusion, the existence of a biological clock implies the oscillations of numerous variables known to affect the breathing pattern; indeed, VT, f, and VE present daily oscillations. The hyperventila-tory responses to hypoxia and hypercapnia, however, remain constant, despite the fact that hypoxia and hypercapnia can have major and differential effects on numerous physiological variables and their circadian patterns.
Seifert EL, Knowles J, Mortola JP: Continuous circadian measurements of ventilation in behaving adult rats. Respir Physiol. 2000, 120: 179-183. 10.1016/S0034-5687(00)00108-0.