Regulation of cardiorespiratory homeostasis in adult and developing rat by catecholamines : effects of hypoxia

Abstract

The aims of the present study were as follow 1) to characterise the neuroplasticity of sympathetic ganglia in the adult rat, after exposure to long-term hypoxia and/or axotomy of the superior cervical ganglion (SCG). The cellular distributions of TH (tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis) and VIP (vasointestinal peptide, which enhances the expression of TH) were examined. In addition, biochemical analyses of catecholamines and VIP were performed in these structures. 2) to investigate the effects of pre- or postnatal hypoxia on maturation of the catecholaminergic structures of the chemoreflex pathway in 1-, 3- and 8- week-old male rats; and, finally, 3) to examine the functional impact of the neural changes observed following prenatal hypoxia by characterising ventilation and cardiac activity.

Results: Effects of axotomy and/or hypoxia on adult rat: In the intact adult rats, hypoxia increased the dopamine level, as well as the density of SIF cells immunostaining for TH and VIP in the SCG. In the axotomized ganglion, hypoxia elicited a 2-fold elevation in the level of VIP, in addition to enhancing the density of neuronal cell bodies immunostaining for this peptide. Thus, the effect of hypoxia on the expression of VIP in neurones was influenced by neural interactions. In the intact stellate ganglion, hypoxia alone induced a 1.5-fold increase in the density of neuronal cell bodies immunostaining for VIP. Thus, ganglia-specific factors appear to play a role in determining the changes in neuronal phenotype which occur in response to hypoxia.

Effects of perinatal hypoxia: 1) Postnatal hypoxia (6 days of exposure to 10% O2, from the first to seventh day of postnatal fife, after which the pups were studied at 3 and 8 weeks of age). Neonatal hypoxia reduced the bodyweight of rats. In sympathetic ganglia, the content and/or turnover rate of norepinephrine was reduced at 3 and 8 weeks of age, but no such changes were observed in the case of dopamine. A long-term disturbance in the activity of the adrenal gland was indicated by the decreases in the content and turnover rate of dopamine in this organ. Neonatal hypoxia also elicited a long-term decrease in the contents and turnover rates of norepinephrine in the heart and lungs. 2) Prenatal hypoxia (pregnant rats exposed to 10% 02, birth under normoxic conditions and pups studied at 1, 3 and 8-9 weeks of age). Prenatal hypoxia decreased the catecholamine content of the carotid bodies for as long as 9 weeks, and the catecholaminergic activity in the A2c, A1, and A5 noradrenergic cell groups of the brainstem until 3 weeks after birth. Rats exposed to prenatal hypoxia hyperventilated until three weeks after birth. Their biphasic ventilatory response to postnatal hypoxia was absent at I week of age and the increase in minute ventilation was enhanced at 3 weeks of age. Prenatal hypoxia increased cardiac variability in the adult offspring.