Kishi Takuya, Hirooka Yoshitaka, Kimura Yoshikuni, Sakai Koji, Ito Koji, Shimokawa Hiroaki, Takeshita Akira
Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Hypertension. 2003 Feb;41(2):255-60. doi: 10.1161/01.hyp.0000050649.30821.cb.
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.
我们之前证明，延髓头端腹外侧区（RVLM）中内皮型一氧化氮合酶（eNOS）的过表达可降低血压、心率（HR）和交感神经活动，并且在易患中风的自发性高血压大鼠（SHRSP）中这些作用会增强。本研究的目的是确定RVLM中由eNOS过表达引起的NO生成增加是否能改善SHRSP中受损的压力感受性反射对心率的控制。我们将编码eNOS的腺病毒载体（AdeNOS）转染到SHRSP或Wistar-Kyoto大鼠（WKY）的RVLM中。在清醒状态下通过无线电遥测系统测量平均动脉压和心率。在基因转移后第7天，通过静脉输注去氧肾上腺素、硝普钠或肼屈嗪来引发心率的反射性变化。与WKY相比，SHRSP中压力感受性反射对心率控制的最大增益显著降低。SHRSP的RVLM中eNOS的过表达改善了受损的压力感受性反射对心率控制的最大增益。用阿托品治疗后，AdeNOS转染组的SHRSP中最大增益仍显著高于未转染组，尽管两组均有所降低。相比之下，用美托洛尔治疗后，两组之间的最大增益没有差异。这些结果表明，RVLM中NO生成的增加改善了SHRSP中受损的压力感受性反射对心率的控制，并且这些作用可能是由于SHRSP的RVLM中NO的心脏交感抑制作用所致。
