Premium
Maintenance of sympathetic nerve discharge and blood pressure in rats exposed to chronic intermittent hypoxia involves enhanced NMDA receptor function in the hypothalamic PVN
Author(s) -
Dong Ying,
Mifflin Steven W,
Toney Glenn M
Publication year - 2009
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.23.1_supplement.792.15
Subject(s) - endocrinology , medicine , nmda receptor , mean arterial pressure , blood pressure , receptor , chemistry , heart rate
Exposure to chronic intermittent hypoxia (CIH) activates the renin‐angiotensin system and raises sympathetic nerve discharge (SND), and mean arterial pressure (MAP). This response profile is consistent with involvement of excitatory forebrain input to the hypothalamic PVN. Here, we investigated control of SND and MAP by PVN NMDA receptors. Control and CIH exposed (3 min 21% O2 ‐ 3 min 10% O2, 8am‐4pm, 7 days) rats were anesthetized and MAP, renal and lumbar SND responses to bilateral PVN injection of the NMDA receptor antagonist AP5 (3.0 nmol in 50 nl/side) were recorded. Baseline MAP was similar across groups. MAP was unchanged by AP5 in control rats (n=4), but decreased by 8 ± 2 mmHg (P<0.05) in the CIH group (n=7). Whereas renal and lumbar SND were not changed by AP5 in control rats, both were reduced (P<0.001) in the CIH group (renal: 83 ± 3, lumbar: 86 ± 1 % baseline). RT‐PCR revealed that NMDA R1 mRNA expression increased by 1.51 ± 0.2 fold in the CIH group compared to controls. We conclude that support of SND and MAP in rats exposed to CIH involves an enhanced role for NMDA receptor activation in the PVN. Similar observations made in other sympathoexcitatory states (e.g., water deprivation, heart failure, AngII‐Salt Hypertension), suggest that similar adaptive processes might underlie PVN‐mediated SND activation in a variety of physiological and disease conditions. Support: P01 HL088052 (SWM & GMT)