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Gene transfer of neuronal nitric oxide synthase to the paraventricular nucleus improves enhanced NMDA NR1 receptor function in rats with chronic heart failure
Author(s) -
Zheng Hong,
Liu Xuefei,
Li Yifan,
Patel Kaushik P
Publication year - 2007
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.21.6.a1267-a
Subject(s) - medicine , microinjection , endocrinology , glutamatergic , nmda receptor , nitric oxide synthase , neuronal nitric oxide synthase , heart failure , nitric oxide , receptor , glutamate receptor , chemistry
Our previous studies have shown that the decreased nitric oxide (NO) and increased glutamatergic mechanisms’ effects on sympathetic regulation within the paraventricular nucleus (PVN) may contribute to the elevated sympathoexcitation during chronic heart failure (CHF). In the present study, we investigated the effects of neuronal NO synthase (nNOS) gene transfer on NMDA NR1 receptor function in the rats with coronary ligation model of CHF. Adenovirus vectors encoding either nNOS (AdnNOS) or β‐galactosidase (AdβGal, as control) were transfected into the PVN in vivo . Three days after application of AdnNOS, the nNOS mRNA expression and protein level were significantly increased within the PVN in rats with CHF (compared to AdβGal‐CHF group, P<0.05). The renal sympathetic nerve activity (RSNA), blood pressure (BP) and heart rate (HR) responses to microinjection of NMDA into the PVN was significantly potentiated (RSNA: 42±2%, P<0.05) in the rats with CHF compared with sham rats. AdnNOS significantly decreased the enhanced RSNA, BP and HR responses to NMDA in the rats with CHF (RSNA: 35±4%, compared to AdβGal‐CHF group, P<0.05). These results indicate that the effects of endogenous nNOS on the glutamatergic mechanism within the PVN may play an important role in the altered balance and tone of sympathetic outflow in the CHF condition.