Premium
Prenatal Nicotinic Exposure (PNE) via Inhibiting the Carotid Body (CB) Induces Depressed Hypoxic Ventilatory Response (dHVR) Dependent On α7nAChRs in Rat Pups
Author(s) -
Zhao Lei,
Zhuang Jianguo,
Ye Chunyan,
Xu Fadi
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.860.4
Subject(s) - carotid body , hypoxic ventilatory response , prenatal exposure , nicotinic agonist , endocrinology , medicine , chemistry , neuroscience , biology , receptor , respiratory system , pregnancy , genetics , electrophysiology , gestation
We have recently reported that PNE with nicotinedelivered via an osmotic minipump (6 mg kg ‐1 d ‐1 ) in utero and postnatal period induces dHVR in P11‐14 rat pups (Zhuang et al., Physiol Report 2014). Here we asked whether: 1) this depression was specific to HVR but not to hypercapnic ventilatory response (HCVR); 2) dHVR resulted from PNE inhibitory effect on the carotid body‐mediated ventilator respone; and 3) α7nAChRs were required to induce dHVR. To this end, HVR (5% O 2 for 5 min) and HCVR (7% CO 2 , 40% O 2 , balanced N 2 for 5 min) were examined by plethysmography in P11‐14 pups prenatally exposed to saline (Ctrl) or nicotine (PNE) ( Series I ). HVR was tested in Ctrl and PNE pups with previous CB ablation ( Series II ) and in the six groups of intact pups: PNE, PNE coupled with mecamylamine, a non‐selective antagonist of nAChRs (MM+PNE), PNE with methyllycaconitine, a selective antagonist of α7nAChR (MLA+PNE), Ctrl, MM+Ctrl, and MLA+Ctrl. As the results, the peak HVR (within 2 min after hypoxia) were ~30% lower in PNE than Ctrl pups (P < 0.01) without significant difference in HCVR between the two groups. CB ablation eliminated HVR in both Ctrl and PNE pups. Neither MM nor MLA had an effect on baseline VE in Ctrl and PNE pups. However, they fully reversed dHVR induced by PNE but did not affect HVR in Ctrl pups. These results suggest that PNE could strikingly blunt HVR via inhibition of the CB‐triggered ventilatory response, which is dependent on activation of α7nAChR (Supported by HL‐107462).