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Chronic inhibition of endothelial nitric oxide synthase activity in nucleus tractus solitarii enhances baroreceptor reflex in conscious rats
Author(s) -
Waki Hidefumi,
Kasparov Sergey,
Wong LiangFong,
Murphy David,
Shimizu Tsuyoshi,
Paton Julian F. R.
Publication year - 2003
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2002.030270
Subject(s) - baroreceptor , nitric oxide synthase , reflex , nitric oxide , nucleus , solitary nucleus , omega n methylarginine , neuroscience , chemistry , medicine , anesthesia , endocrinology , biology , heart rate , blood pressure
In acute experiments, we demonstrated previously that nitric oxide (NO) donors exogenously applied to the nucleus tractus solitarii (NTS) depressed the baroreceptor cardiac reflex. In this study, we determined a role for endogenous endothelial nitric oxide synthase (eNOS) activity in the NTS for chronically regulating baroreceptor reflex function in conscious rats. A recombinant adenoviral vector directing expression of a truncated form of eNOS was microinjected bilaterally into the NTS to inhibit endogenous eNOS activity. Arterial pressure was monitored continuously using radio‐telemetry in freely moving animals and spontaneous baroreceptor reflex gain (sBRG) determined by a time‐series method. sBRG showed a gradual increase from day 7 to 21 after gene transfer and the value at day 21 (1.68 ± 0.20 ms mmHg −1 , n = 6 ) was significantly higher than that before gene transfer (1.13 ± 0.09 ms mmHg −1 , P < 0.001 ). This value was also significantly higher than that in rats in which enhanced green fluorescent protein (eGFP) was expressed in the NTS (1.04 ± 0.21 ms mmHg −1 ; n = 6 , P < 0.01 ) and saline‐treated groups (1.12 ± 0.15 ms mmHg −1 ; n = 4 , P < 0.05 ), which did not change from control levels. In addition, heart rate decreased from 336 ± 6 to 318 ± 8 b.p.m. ( P < 0.05 ) 21 days after gene transfer. This value was also significantly lower than that in control groups (eGFP: 348 ± 9 b.p.m., n = 6 , P < 0.01 ; saline: 347 ± 5 b.p.m., n = 4 , P < 0.05 ). Gene transfer did not affect arterial pressure. These findings suggest that in the conscious rat eNOS is constitutively active within the NTS and is a factor regulating baroreceptor reflex gain and heart rate.