Site(s) and mechanism of changes in arterial chemo-sensitivity after carotid (CBD) and/or aortic (AOD) denervation

Through injections of NaCN at various locations in awake piglets and rats, we gained insight into the plasticity of arterial chemosensitivity. Less than 8 day old piglets exhibited both carotid and aortic chemosensitivity. The aortic chemosensitivity persisted after 8 days only if CBD had been performed, but CBD after 8 days of age resulted in restoration of aortic chemosensitivity. At the site of aortic chemosensitivity, there was greater serotonin (5-HT) immunoreactivity in CBD than in carotid intact piglets and this increase was dependent upon intact aortic innervation. Intravenous injections of the 5-HT5a receptor antagonist, methiotepin, prior to the NaCN injection eliminated aortic chemosensitivity. Western blots indicated the expression of the 5-HT5a receptors at this aortic site and the protein existed equally in CBD and carotid intact piglets. AOD+CBD resulted in chemosensitivity in the left ventricle which was attenuated by prior injection of the 5-HT5a receptor antagonist. Neonatal and adult rats also developed aortic chemosensitivity after CBD. These data indicate there are multiple sites for plasticity in arterial chemosensitivity, which appears to involve upregulation of serotonin acting at the 5-HT5a receptors.