Carotid body mechanisms in acclimatization to hypoxia

Most studies oriented toward examining mechanisms increasing carotid body ( CB) sensitivity to hypoxia during ventilatory acclimatization (VAH) have fo cussed on the role of known neuromodulators of CB function. Two general cat egories of the neuromodulatory agents studied most extensively could be con sidered: those thought to be primarily inhibitory to CB function: dopamine, norepinephrine, nitric oxide and those thought to be primarily excitatory: substance P, endothelin. There is evidence that these putative inhibitory agents are up-regulated in the first weeks of chronic hypoxia and that subs tance P is down-regulated. All these changes would favor a decrease in CB s ensitivity to hypoxia. There are data suggesting that CB endothelin activit y is up-regulated in rats subjected to chronic hypoxia, a direction suggest ing increased CB sensitivity to hypoxia. Dopamine may have an excitatory as well as an inhibitory role on the CB, but there is not yet evidence to ind icate that an excitatory role for DA exists in chronic hypoxia. Ion channel studies of type I CB cells suggest increased excitability after prolonged hypoxia. The role of excitatory CB nicotinic receptors and putative seroton in type 3 receptors should be examined further for their potential role in VAH. It is suggested that a balance of excitatory and inhibitory modulation is responsible for increased CB sensitivity to hypoxia during VAH. (C) 200 0 Elsevier Science B.V. All rights reserved.