Neurochemical and Molecular Biological Aspects on the Resetting of the Arterial Chemoreceptors in the Newborn Rat

Abstract

The role of the carotid body chemoreceptors in the fetus and immediately newborn has been a matter of debate over the past decades. Studies on fetal sheep suggested that the chemoreceptors are active in utero (Barcroft and Karvonen, 1948; Itskovitz and Rudolph, 1982, 1987), and this was confirmed by direct recordings from the sinus nerve (Blanco et al., 1984). However, the chemoreceptor response to hypoxia was lower in the fetus than in the newborn lamb (Blanco et al., 1984). This is consistent with the observation that the strength of the chemoreflex response is increased in babies a few days after birth as compared to the immediately newborn (Hertzberg and Lagercrantz, 1987). Thus, the arterial chemoreceptors seem to adapt from the low PaO₂ prevalent in utero and reset their sensitivity after birth, when arterial oxygen tension is rising. As a consequence, the chemoreceptors are quiescent during the first day or so after birth. Accordingly, onset of breathing after birth appear to be dependent on other drive mechanisms, e.g. thermal, visual and tactile stimuli. The postnatal resetting of the chemoreceptors has been hypothesized to be due to changes in neurotransmitter expression and turnover in the carotid body. Substance P and the catecholamines are currently among the most studied messenger molecules. Substance P-like immunoreactivity was found in nerve fibers prenatally, while immunoreactive cells were not seen until after birth in kittens (Scheibner et al., 1988). In the adult cat the stimulation of carotid body chemoreceptors by hypoxia, but not by hypercapnia, was blocked by a substance P-antagonist (Prabhakar et al., 1984, 1987). Dopamine, the most abundant catecholamine in the carotid body of most species, has been shown to modulate chemoreceptor activity (Cardenas and Zapata, 1981; see also Hellstrom et al., 1984). In the following we would like to discuss some experiments aiming to define the role of these two neurotransmitters in the carotid body.