CHANGES IN TYROSINE-HYDROXYLASE AND SUBSTANCE-P IMMUNOREACTIVITY IN THE CAT CAROTID-BODY FOLLOWING CHRONIC HYPOXIA AND DENERVATION

Long-term hypoxia elicits functional changes in the cat carotid body w hich are manifest as altered chemosensitivity in response to hypoxia. Previous studies have suggested that these functional adjustments may be mediated by changes in neurotransmitter levels in chemosensory type I cells. Neurotransmitter metabolism in the carotid body has also bee n shown to be regulated by the neural innervation to the organ. The pr esent study using the cat carotid body demonstrates profound changes i n the levels of immunoreactivity of the catecholamine-synthesizing enz yme, tyrosine hydroxylase, and the neuropeptide, substance P, in respo nse to a two-week exposure to hypoxia (10% O-2 in 90% N-2). Furthermor e, these changes were modulated both by sensory and sympathetic denerv ation of the organ. For TH, the intensity of immunostaining in type I cells was markedly increased by long-term hypoxia in both normal and c hronic carotid sinus nerve-denervated carotid bodies, but this effect was blocked following chronic sympathectomy. Substance P immunoreactiv ity in type I cells was dramatically attenuated by hypoxia in both int act and chronic carotid sinus nerve-denervated preparations, but this effect was reduced following chronic sympathectomy. Tyrosine hydroxyla se-and substance P-positive axon terminals were observed to innervate type I cells. These axons were also present in chronically sympathecto mized preparations, but they disappeared following chronic carotid sin us nerve-denervation suggesting that they very likely arise from senso ry neurons in the petrosal ganglion. Our data indicate that chronic ch emoreceptor stimulation by hypoxia elicits multiple neurochemical adju stments in the cat carotid body. These changes suggest that catecholam inergic enzymes and neuropeptides play a significant role in the adapt ive mechanisms of chemoreceptor function which occur in response to ch ronic physiological stimulation. Furthermore, the data suggest that ne urotrophic mechanisms may influence neurotransmitter metabolism in che mosensory type I cells. (C) 1998 IBRO. Published by Elsevier Science L td.