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Published Online
on January 6, 2003

Hypertension. 2003
Published online before print January 6, 2003, doi: 10.1161/01.HYP.0000050649.30821.CB
A more recent version of this article appeared on February 1, 2003
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Submitted on June 18, 2002
Revised on July 2, 2002

Overexpression of eNOS in RVLM Improves Impaired Baroreflex Control of Heart Rate in SHRSP

Takuya Kishi; Yoshitaka Hirooka*; Yoshikuni Kimura; Koji Sakai; Koji Ito; Hiroaki Shimokawa; and Akira Takeshita

From the Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.

* To whom correspondence should be addressed. E-mail: hyoshi{at}cardiol.med.kyushu-u.ac.jp.

Abstract—We previously demonstrated that the overexpression of endothelial nitric oxide synthase (eNOS) in the rostral ventrolateral medulla (RVLM) decreases blood pressure, heart rate (HR), and sympathetic nerve activity and that these effects are enhanced in stroke-prone spontaneously hypertensive rats (SHRSP). The aim of this study was to determine if an increase in NO production in the RVLM caused by the overexpression of eNOS improves the impaired baroreflex control of HR in SHRSP. We transfected adenovirus vectors encoding eNOS (AdeNOS) into the RVLM of SHRSP or Wistar-Kyoto rats (WKY). Mean arterial pressure and HR were measured by a radio-telemetry system in the conscious state. Reflex changes in HR were elicited by intravenous infusion of either phenylephrine, sodium nitroprusside, or hydralazine at day 7 after the gene transfer. The maximum gain of the baroreflex control of HR was significantly decreased in SHRSP compared with WKY. Overexpression of eNOS in the RVLM of SHRSP improved the impaired maximum gain of the baroreflex control of HR. After treatment with atropine, the maximum gain was still significantly greater in SHRSP in the AdeNOS-transfected group than in the nontransfected group, although it was decreased in both groups. In contrast, after treatment with metoprolol, the maximum gain did not differ between the two groups. These results indicate that an increase in NO production in the RVLM improves the impaired baroreflex control of HR in SHRSP and that these effects may have resulted from a cardiac sympathoinhibitory effect of NO in the RVLM of SHRSP.


Key words: genes • nitric oxide • sympathetic nervous system • brain • baroreflex




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