Differences in time-dependent hypoxic phrenic responses among inbred rat strains

Abstract

. Differences in time-dependent hypoxic phrenic responses among inbred rat strains. J Appl Physiol 98: 838 -844, 2005. First published November 5, 2004; doi:10.1152 doi:10. /japplphysiol.00984.2004 responses differ between rodent strains, suggesting a genetic contribution to interindividual variability. However, hypoxic ventilatory responses consist of multiple time-dependent mechanisms that can be observed in different respiratory motor outputs. We hypothesized that strain differences would exist in discrete time-dependent mechanisms of the hypoxic response and, furthermore, that there may be differences between hypoglossal and phrenic nerve responses to hypoxia. Hypoglossal and phrenic nerve responses were assessed during and after a 5-min hypoxic episode in anesthetized, vagotomized, and ventilated rats from four inbred strains: Brown Norway (BN), Fischer 344 (FS), Lewis (LW), and Piebald-viral-Glaxo (PVG). During baseline, burst frequency was higher in PVG than LW rats (P Ͻ 0.05), phrenic burst amplitude was higher in PVG vs. other strains (P Ͻ 0.05), and hypoglossal burst amplitude was higher in PVG and BN vs. FS and LW (P Ͻ 0.05). During hypoxia, burst frequency did not change in BN or LW rats, but it increased in PVG and FS rats. The phrenic amplitude response was smallest in PVG vs. other strains (P Ͻ 0.05), and the hypoglossal response was similar among strains. Short-term potentiation posthypoxia was slowest in FS and fastest in LW rats (P Ͻ 0.05). Posthypoxia frequency decline was absent in PVG, but it was observed in all other strains. Augmented breaths were observed during hypoxia in FS rats only. Thus genetic differences exist in the time domains of the hypoxic response, and these are differentially expressed in hypoglossal and phrenic nerves. Furthermore, genetic diversity observed in hypoxic ventilatory responses in unanesthetized rats may arise from multiple neural mechanisms. hypoxia; breathing; hypoglossal; genetic BOTH EXPERIENCE (i.e., plasticity; reviewed in Ref. 29) and genetics (reviewed in Ref. 17) influence the neural control of breathing. Genetic influences on respiratory control have been described in rats (13,15,20,37), mice (40), and humans (42). Because rats are commonly used to investigate fundamental aspects of breathing, an understanding of the genetic determinants of ventilatory control in this species is essential. Furthermore, understanding of the range of genetic variation in respiratory control may have important clinical implications in a genetically diverse population, such as humans.Differences in ventilation among inbred and outbred rat strains have been documented during eupnea (quiet breathing), hypoxia, hypercapnia, and exercise (13,20,37), and some of these changes have been associated with genotypic differences, localized to specific chromosomes (13). For example, in Brown Norway (BN) rats the frequency response to hypoxia is small compared with some other strains (20, 37). Hodges et al. (20) reported that, although BN rats responded to hypoxia with less change...

Phrenic Motoneuron Discharge Patterns During Hypoxia-Induced Short-Term Potentiation in Rats

“…However, prior work indicated that moderate CO 2 reductions during hypoxia do not prevent respiratory STP (Song and Poon 2009), and indeed, a robust STP of phrenic activity was observed during and after hypoxia. In addition, the magnitude of the acute hypoxic phrenic response reported here is both quantitatively and qualitatively similar to prior reports in which strict isocapnia was maintained (Fuller 2005;Golder et al 2005). Finally, we confirmed in additional experiments that the drop in PaCO 2 during hypoxia did not significantly alter the expression of phrenic STP.…”

“…The potential impact of urethane anesthesia on STP is not certain. However, respiratory STP occurs in both anesthetized animals (e.g., current data; Golder et al 2005;Hayashi et al 1993) and conscious humans (Fregosi 1991) and animals (Kline et al 2002;McGuire 2008). Urethane was selected as the anesthetic in this study because robust hypoxic phrenic responses occur in urethane anesthetized rats (Bach and Mitchell 1996;Baker-Herman et al 2004).…”

“…Respiratory STP has been observed in both vagal intact (Xi et al 1993) and vagotomized conditions (Golder et al 2005;Hayashi et al 1993;Wagner and Eldridge 1991). However, vagal afferent feedback probably attenuates the expression of phrenic STP.…”

Morphometric analysis of the phrenic nerve in male and female Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR)

“…Differences among inbred rat strains (1), as well as differences between inbred and outbred rat strains (2), have been documented during eupnea, hypoxia, hypercapnia, and exercise (2,3). Some of these differences are associated with genotypic differences localized on specific chromosomes (3).…”

Genetic determinants on rat chromosome 6 modulate variation in the hypercapnic ventilatory response using consomic strains

“…Strain differences in the acute response to hypoxia (11,25), hypercapnia (12,18), episodic hypoxia (3), and the posthypoxic frequency response (2,19) have been reported suggestive of a genetic component to these responses. Several studies involving the control of breathing in inbred strains of mice have identified regions on mouse chromosomes 1, 3, 5, and 9 to which specific breathing phenotypes can be linked (17,20,22,23).…”