Ventilatory acclimatization

Bisgard GE. The role of arterial chemoreceptors in ventilatory acclimatization to h poxia. In O Regan RG, Nolan P, McQueen DS, Paterson DJ, eds. Advances in Experimental Medicine and Biology. Vol. 360, Arterial Chemoreceptors Cell to System. New York Plenum Press, 1994 109-122. 

Powell FL, Huey KA, Dwinell MR. Central nervous system mechanisms of ventilatory acclimatization to hypoxia. Respir Physiol 2000 121(2-3) 223-236. 

Tatsumi K, Pickett CK, Weil JV Possible role of dopamine in ventilatory acclimatization to high altimde. Respir Physiol 1995 99 63-73. 

The ventilatory acclimatization to hypoxia is almost exclusively dependent on the carotid bodies as demonstrated by two studies carried out on sheep showing that HVA is not achieved after chemodenervation (8), but ean be indueed by perfusion of the carotid bodies with hypoxic normocapnic blood (9). The drop of arterial oxygen tension consecutive to hypoxic exposure induces a caseade of events— whieh is still not fully understood—leading to the associated anatomieal, neurochemical, and functional changes within the carotid bodies. 

The functional changes within the carotid bodies are tightly connected to the anatomical and neurochemical changes occurring imder chronic hypoxia. If some results show decreased carotid body hypoxic sensitivity after chronic hypoxia (22), it is now well established that successful ventilatory acclimatization relies on an increased sensitivity of carotid body chemoreceptors. Actually, numerous experimental approaches, ranging from hypoxic ventilatory response in awake animals (10,23) to in vitro measurements of ion channel function on glomic cells (24), are consistent with increased carotid body sensitivity following chronic hypoxia. 

A proper acclimatization to hypoxia is very important and determines the overall ability to cope with hypoxia. In climbers at very high altitude, the maximum altitude that an individual can reach is clearly related to the hypoxic ventilatory response measured at sea level and to the extent of the ventilatory acclimatization during ascension (46,46a). At lower altitude, a proper ventilatory acclimatization is also a determinant mechanism for the overall hypoxic acclimatization. Our own observations (unpublished) in rats permanently living at 3600 m above sea level (Bolivian Institute for Altitude Biology—IBBA, La Paz, Bolivia) revealed that following surgical chemodenervation, the hematocrit rose from a baseline level of around 50% to more than 70% within a few weeks and numerous animals died during this period. 

Thus, a transitory insensitivity to dopamine appeared during the first days of hypoxia, and central dopamine contributes to ventilatory acclimatization between 2 and 8 days of hypoxia. The level of mRNA encoding dopamine D2 receptors was initially increased in the caudal NTS within the first 12 hr of hypoxia and then decreased below control levels within the next 7 days (36). These time-dependent changes in dopamine D2 receptors could also contribute to HVA. 

Chemosensory mechanisms in the NTS of rat can develop following irreversible disruption of the chemoafferent pathway. Ventilatory acclimatization to hypoxia was altered but still persisted in carotid sinus nerve-transected rats (106). Since the caudal NTS is a major site of integration for peripheral chemosensory inputs, it is worth noting that the hypoxia-induced increase in tyrosine hydroxylase (TH) mRNA in caudal NTS was not impaired by carotid chemodenervation (106). On the other hand, transsynaptic activation by carotid body inputs is a key element in the changes of norepinephrine turnover during long-term hypoxia since carotid body... 

Smith C, Bisgard G, Nielsen A, Daristotle L, Kressin N, Forster H, Dempsey J. Carotid bodies are requiered for ventilatory acclimatization to chronic h q)oxia. J Appl Physiol 1986 60 1003-1010. 

Busch MA, Bisgard GE, Forster HV Ventilatory acclimatization to h3q)oxia is not dependant on arterial h q)oxemia. J Appl Physiol 1985 58 1874-1880. 

Ryan ML, Hedrick MS, Pizarro J, Bisgard GE. Carotid body noradrenergic sensitivity in ventilatory acclimatization to hypoxia. Respir Physiol 1993 92 77-90. 

Schmitt P, Soulier Y, Pequignot JM, Pujol JF, Denavit-Sauhie M. Ventilatory acclimatization to chronic hypoxia relationship to noradrenaline metabohsm in the rat solitary complex. J Physiol (Lond) 1994 477 331-337. 

Fatemian M, Kim DY, Poulin MJ, Robbins PA. Very mild exposure to hypoxia for 8 h can induce ventilatory acclimatization in humans. Pfiugers Arch 2001 441 840— 843. 

Engwall MJA, Bisgard GE. Ventilatory responses to chemoreceptor stimulation after hypoxic acclimatization in awake goats. J Appl Physiol 1990 69 1236-1243. 

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