Chronic inhibition of endothelial nitric oxide synthase activity in nucleus tractus solitarii enhances baroreceptor reflex in conscious rats.
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.
Waki
Hidefumi
H
Department of Physiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK.
Kasparov
Sergey
S
Wong
Liang-Fong
LF
Murphy
David
D
Shimizu
Tsuyoshi
T
Paton
Julian F R
JF
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002317:Cardiovascular Agents / Q000494:pharmacology; D018014:Gene Transfer Techniques; D006339:Heart Rate / Q000502:physiology; D008297:Male; D008845:Microinjections; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D017208:Rats, Wistar; D017552:Solitary Nucleus / Q000201:enzymology*; D013997:Time Factors; D014162:Transfection
D002317:Cardiovascular Agents; D000804:Angiotensin II; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat