Postnatal developmental changes in CO₂sensitivity in rats

Abstract

Ventilatory sensitivity to CO(2) in awake adult Brown Norway (BN) rats is 50-75% lower than in adult Sprague-Dawley (SD) and salt-sensitive Dahl S (SS) rats. The purpose of the present study was to test the hypothesis that this difference would be apparent during the development of CO(2) sensitivity. Four litters of each strain were divided into four groups such that rats were exposed to 7% inspired CO(2) for 5 min in a plethysmograph every third day from postnatal day (P) 0 to P21 and again on P29 and P30. From P0 to P14, CO(2) exposure increased pulmonary ventilation (Ve) by 25-50% in the BN and SD strains and between 25 to over 200% in the SS strain. In all strains beginning around P15, the response to CO(2) increased progressively reaching a peak at P19-21 when Ve during hypercapnia was 175-225% above eucapnia. There were minimal changes in CO(2) sensitivity between P21 and P30, and at both ages there were minimal between-strain differences. At P30, the response to CO(2) in the SS and SD strains was near the adult response, but the response in the BN rats was 100% greater at P30 than in adults. We conclude that 1) CO(2)-sensing mechanisms, and/or mechanisms downstream from the chemoreceptors, change dramatically at the age in rats when other physiological systems are also maturing ( approximately P15), and 2) there is a high degree of age-dependent plasticity in CO(2) sensitivity in rats, which differs between strains.

Characterization of the chemosensitive response of individual solitary complex neurons from adult rats

“…We found that SC neurons from adult rats had a maintained acidification with a lack of pH i recovery in response to HA, which is similar to what has been found in SC neurons from neonates (23,42), and that the percentage of SC neurons activated or inhibited by HA and the magnitude of these responses were unchanged in adult rats compared with neonates (5). This developmental profile did not coincide with previously described patterns for the development of the rat ventilatory response to hypercapnia (6,49).…”

“…It is instructive to compare this pattern of early maturity of chemosensitivity in putative chemosensitive neurons with the early developmental pattern of the whole animal ventilatory response to inspired CO 2 . The exact pattern of this development is uncertain, being either triphasic with a minimum point at about P5-P10 (49) or involving a dramatic increase in the hypercapnic ventilatory response from P15 to P20 (6). Both of these patterns show an increase in the ventilatory response to hypercapnia between P10 and P15 that agrees with the development of chemosensitivity in serotonergic medullary raphé neurons (53).…”

“…The response of adult SC neurons to HA has been studied (7, 10, 21, 23) but has not been well quantified with respect to the percentage and magnitude of chemosensitive neuronal responses or with respect to the response of pH i in these neurons to HA. Obtaining the full developmental profile of chemosensitive neurons into adulthood will enable us to compare the developmental profile of these neurons with the developmental profile of the ventilatory response to hypercapnia in the intact animal (6,49). In this way, we may be able to gain insights into the role played by different central chemosensitive regions in the overall respiratory network and in the control of ventilation.…”

The ventilatory response to hypoxia and hypercapnia is absent in the neonatal fat-tailed dunnart

“…The respiratory response to reduced O 2 (hypoxia) or increased CO 2 (hypercapnia) is dependent on the relative size and maturity of the species at birth, and generally increases with postnatal age (Bonora et al, 1994), in part as a result of the increasing sensitivity of both central and peripheral chemoreceptors (Hanson et al, 1989;Davis et al, 2006). In contrast to the adult, the newborn typically does not sustain an increase in minute ventilation (V E ; hyperpnoea) in response to hypoxia, and in some cases V E during hypoxia falls below pre-hypoxic levels (Neubauer et al, 1990).…”

“…Despite the reduced breathing in newborns subjected to acute hypoxia, they still hyperventilate because of a larger drop in the rate of oxygen consumption (V O2 ) compared with V E . While the hypercapnic ventilatory response of most newborn species is reduced compared with that of adults Davis et al, 2006), unlike hypoxia, it is sustained over time by a persistent increase in tidal volume (V T ), despite a gradual decline in the initial respiratory frequency (f) increase (Bonora et al, 1994;Cummings and Frappell, 2009). Exceptions to these patterns exist, however, with the neonatal North American opossum (another marsupial) demonstrating an unusually large ventilatory response to hypoxia and a hypometabolic response to hypercapnia (Farber, 1972), which attenuates with age .…”