Effects of carotid sinus nerve transection on changes in neuropeptide Y and indolamines induced by long-term hypoxia in rats

Abstract

Long-term hypoxia induces changes in neuropeptide-Y-like immunoreactivity (NPY-LI) and/or in the content of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) at the central level. To determine whether these alterations depend on the integrity of carotid body (CB) chemoreceptors, intact rats or those whose carotid sinus nerve was transected (CSNT) were exposed to hypoxia (10% O2) or to normoxia for 14 days. Thereafter, NPY-LI, 5-HT and 5-HIAA levels in discrete brain regions were determined. The increase in NPY-LI in the ventrolateral medulla oblongata (VLM) of intact hypoxic rats was mostly abolished after CSNT and therefore is mainly mediated by CB chemoreceptors. In contrast, other hypoxia-induced changes were similar or even enhanced in CSNT as compared to intact rats and therefore do not depend on the integrity of CB chemoreceptors. This was the case for the increase of NPY-LI in the striatum and the caudal dorsomedian medulla oblongata (DMM), as well as for all the changes in 5-HT and 5-HIAA in the DMM, the VLM, the raphe nuclei, the striatum and the frontal cortex. We propose that long-term hypoxia alters brain NPY-LI and indolamine content through the stimulation of CB chemoreceptors or ancillary chemoreceptors, as well as through local biochemical or morphological mechanisms.

Altered daily rhythms of brain and pituitary indolamines and neuropeptides in long-term hypoxic rats

“…Several hypotheses could be raised to explain how acute or chronic hypoxia alters daily rhythms. First, carotid body chemoreceptors or ancillary central O 2 sensors, which may have a role in hypoxia-induced changes in basal level of neurotransmitters (23), could also be involved in the alteration of their daily rhythmicity. Local biochemical mechanisms could also be involved, especially through proteins such as hypoxiainducible factor 1 (HIF-1) (33), which may interact with the expression of genes regulating circadian rhythms (11,32).…”

“…Indeed, catecholamine and indolamine metabolism, as well as the concentration of some neuropeptides, are altered in discrete brain areas during chronic hypoxia in the rat (22,24,25,30). Furthermore, some of these neurochemical alterations may be linked to the chemoreflex activation and the sympathetic hyperactivity that are known to be present in long-term hypoxic animals (23,30).…”

Chronic hypoxia inhibits the antihypertensive effect of melatonin on pulmonary artery

“…It was demonstrated that hypoxia decreased the circulating levels of serotonin (the precursor of melatonin) by about 30% in different regions of the brain in rats, which would certainly influence the levels of melatonin and, thereby, its effect on cardiovascular system [20,22]. Despite a large volume of work on melatonin, its role in the cardiovascular system, particularly under hypoxic conditions, is poorly understood and its effect on hypoxic pulmonary hypertension has not been studied before.…”

“…Long-term hypoxia has been demonstrated to alter the brain indoleamine concentrations [20] and have an inhibitory effect on melatonin secretion [21]. It was demonstrated that hypoxia decreased the circulating levels of serotonin (the precursor of melatonin) by about 30% in different regions of the brain in rats, which would certainly influence the levels of melatonin and, thereby, its effect on cardiovascular system [20,22].…”