Three-dimensional analysis and molecular mechanism of the peptidergic innervation in the arterial chemoreceptor organ

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The carotid bodies, which are the primary sensory organs for sensing changes in arterial blood gases and hydrogen ion concentration, were enlarged in the rat exposed to chronic isocapnic hypoxia (10% 02 in N2 and 3-4% C02 for 3 months). The peptidergic innervation in the enlarged carotid bodies was different from that in the normoxic control carotid bodies. The density of SP and CGRP fibers in the chronically hypoxic carotid body decreased significantly to under 50 %, the density of VIP fibers increased significantly 1.80 times, and the density of NPY fibers were unchanged. Three-dimensional analysis showed that these peptidergic fibers are mainly associated with expanded vasculatures. In addition, the density of NOS-containing nerve fibers in the hypoxic carotid bodies was significantly decreased. These morphological results suggest that altered innervation of the chronica1ly hypoxic carotid body is one feature of hypoxic adaptation. Because these neuropeptides are vasoactive in nature, altered carotid body circulation may contribute to modulation of the chemosensory mechanisms by chronic hypoxia, and because it has been considered that nitric oxide (NO) is an inhibitory neuronal messenger in the normoxic carotid body, the present findings suggest that the sensory mechanisms in the hypoxic carotid body may be involved in 'disinhibition' resulting from reduced NO synthesis.Hypoxic and chemical stimuli increased intracellular Ca^<2+> in the glomus cells (chemoreceptor cells), but did not increase intracellular Ca^<2+> in about 20% of glomus cells in the cluster. These physiological results suggest that free Ca^<2+> may be produced from intracellular binding Ca^<2+> in response to the stimuli, and also that glomus cells with increased intracellular Ca^<2+> may hyperpolarize through the activation of calcium-dependent potassium channels.