Hyperoxia-induced developmental plasticity of the hypoxic ventilatory response in neonatal rats: contributions of glutamate-dependent and PDGF-dependent mechanisms
Bavis, RW; Deangelis, KJ; Horowitz, TC; Reedich, LM; March, RJ
HERO ID
2232214
Reference Type
Journal Article
Year
2014
Language
English
PMID
| HERO ID | 2232214 |
|---|---|
| In Press | No |
| Year | 2014 |
| Title | Hyperoxia-induced developmental plasticity of the hypoxic ventilatory response in neonatal rats: contributions of glutamate-dependent and PDGF-dependent mechanisms |
| Authors | Bavis, RW; Deangelis, KJ; Horowitz, TC; Reedich, LM; March, RJ |
| Journal | Respiratory Physiology and Neurobiology |
| Volume | 191 |
| Page Numbers | 84-94 |
| Abstract | Rats reared in hyperoxia exhibit a sustained (vs. biphasic) hypoxic ventilatory response (HVR) at an earlier age than untreated, Control rats. Given the similarity between the sustained HVR obtained after chronic exposure to developmental hyperoxia and the mature HVR, it was hypothesized that hyperoxia-induced plasticity and normal maturation share common mechanisms such as enhanced glutamate and nitric oxide signaling and diminished platelet-derived growth factor (PDGF) signaling. Rats reared in 21% O2 (Control) or 60% O2 (Hyperoxia) from birth until 4-5 days of age were studied after intraperitoneal injection of drugs targeting these pathways. Hyperoxia rats receiving saline showed a sustained HVR to 12% O2, but blockade of NMDA glutamate receptors (MK-801) restored the biphasic HVR typical of newborn rats. Blockade of PDGF-β receptors (imatinib) had no effect on the pattern of the HVR in Hyperoxia rats, although it attenuated ventilatory depression during the late phase of the HVR in Control rats. Neither nitric oxide synthase inhibitor used in this study (nNOS inhibitor I and l-NAME) altered the pattern of the HVR in Control or Hyperoxia rats. Drug-induced changes in the biphasic HVR were not correlated with changes in metabolic rate. Collectively, these results suggest that developmental hyperoxia hastens the transition from a biphasic to sustained HVR by upregulating glutamate-dependent mechanisms and downregulating PDGF-dependent mechanisms, similar to the changes underlying normal postnatal maturation of the biphasic HVR. |
| Doi | 10.1016/j.resp.2013.11.006 |
| Pmid | 24284036 |
| Wosid | WOS:000331028800011 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Keyword | Biphasic hypoxic ventilatory response; Hypoxic ventilatory depression; NMDA glutamate receptor; PDGF-beta receptor; Nitric oxide synthase; Heterokairy |