Article

Cardiovascular effects of overexpression of endothelial nitric oxide synthase in the rostral ventrolateral medulla in stroke-prone spontaneously hypertensive rats

Kyushu University, Hukuoka, Fukuoka, Japan
Hypertension (Impact Factor: 6.48). 03/2002; 39(2):264-8. DOI: 10.1161/hy0202.102701
Source: PubMed

ABSTRACT

We have previously demonstrated that the overexpression of endothelial NO synthase (eNOS) in the rostral ventrolateral medulla (RVLM) decreases blood pressure, heart rate, and sympathetic nerve activity via an increase in gamma-amino butyric acid release in normotensive Wistar-Kyoto rats (WKY). Stroke-prone spontaneously hypertensive rats (SHRSP) appear to have reductions of NO production and GABA release in the RVLM. The aim of this study was to determine whether the effects of the increase in NO production in the RVLM in SHRSP are different from those in WKY. We transfected adenovirus vectors encoding either eNOS (AdeNOS) or beta-galactosidase (Adbetagal) into the RVLM of both strains. In the AdeNOS-treated group, mean arterial blood pressure and heart rate in the conscious state were significantly decreased at day 7 after the gene transfer in both strains. The decreases in mean arterial blood pressure and heart rate were significantly greater in SHRSP than in WKY. Urinary norepinephrine excretion was also decreased to a greater degree in SHRSP than in WKY after the gene transfer. The pressor response evoked by bicuculline into the RVLM of WKY was greater than that of SHRSP in the nontransfected group. However, in the AdeNOS-treated group, the pressor response did not differ between SHRSP and WKY after the gene transfer. These results indicate that the increase in NO production evoked by the overexpression of eNOS in the RVLM causes greater depressor and sympathoinhibitory responses in SHRSP than in WKY by improving an inhibitory action of GABA on the RVLM neurons.

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Available from: Takuya Kishi, Oct 01, 2015
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    • "It is likely that the RVLM NO effect on BP depends on the source of NO and its effect on local sympathoinhibitory (GABA) and sympathoexcitatory (L-glutamate) neuromodulators . For example, although GABA inhibition is implicated in the NO-dependent CB 1 R-mediated pressor response (Ibrahim and Abdel-Rahman, 2012), eNOS-derived NO mediates increases in the RVLM GABA level and hypotension (Kishi et al., 2001Kishi et al., , 2002). More studies are warranted to delineate the mechanisms of the differential role of RVLM NO in modulating sympathetic activity/BP and to investigate the possibility that GPR18- dependent NO generation enhances RVLM GABA release/ signaling in future studies. "
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    • "In the brain, the balance between excitatory and inhibitory amino acids determines the neural activity (Li et al., 2002; Garthwaite, 2008). In hypertensive rats, inhibitory amino acid γ-amino butylic acid (GABA) in the RVLM is decreased (Kishi et al., 2002), which in part contributes to the activation of the SNS. NO in the RVLM increases GABA release (Kishi et al., 2001). "
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    • "Controversy remains as to whether endogenous nitric oxide (NO) decreases SNA. Some reports show that NO decreased the activities of RVLM neurons and sympathetic outflow.43, 44 In contrast, Kimura et al.45 reported that NO produced by inducible NOS in the RVLM contributed to high BP of SHR. "
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