Volume 11 Issue 4 - November 6, 2009 PDF
Adenosine Modulates Cardiovascular Functions Through Activation of Extracellular Signal-Regulated Kinases 1 and 2 and Endothelial Nitric Oxide Synthase in the Nucleus Tractus Solitarii of Rats
Wen-Yu Ho1, Pei-Jung Lu5,*, Michael Hsiao3, Hwong-Ru Hwang4, Yu-Chou Tseng7, Mao-Hsiung Yen2, Ching-Jiunn Tseng2,6,8

1 Institute of Medical Sciences , National Defense Medical Center, Taipei, Taiwan
2 Department of Pharmacology , National Defense Medical Center, Taipei, Taiwan
3 Genomics Research Center, Academia Sinica, Taipei, Taiwan
4 Department of Internal Medicine and Department of Medical Education and Research , Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
5 Institute of Clinical Medicine National Cheng Kung University, Tainan, Taiwan
6 Institute of Biomedical Sciences , National Sun Yat-sun University, Kaohsiung, Taiwan
7 Department of Pharmacology, National Cheng Kung University, Tainan, Taiwan
8 Institute of Clinical Medicine , National Yang-Ming University, Taipei, Taiwan
* pjlu2190@mail.ncku.edu.tw

Circulation 2008;117;773-780

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Dr. Pei-Jung Lu
Nucleus tractus solitarii (NTS) locates in the brain stem which is the central cardiovascular control center and have been demonstrated to play an important role in the cardiovascular regulation. Our previous study also demonstrated that the cardiovascular regulatory effects of insulin in the NTS were accomplished through activating PI3K-PKB/Akt-NO signaling pathways. Adenosine has been shown to play an important role in central cardiovascular control that microinjection of adenosine into NTS produces slowly developed long-lasting (minutes) and dose-related decreases in blood pressure (BP) and heart rate (HR). The molecular mechanism however remained to be clarified. In this study, we performed intra-NTS microinjection of adenosine and examined its effect in blood pressure (BP) and heart rate (HR). Moreover, we examined the downstream signal molecules involved in the adenosine mediated cardiovascular regulation by immunohistochemistry and immunobloting analyses. Two conclusions can be drawn from this study. First, Adenosine-ERK-eNOS signaling was confirmed in neuronal cells of NTS. Second, Adenosine induced the phosphorylation and activation of ERK and eNOS can cause the increase the NO amount in NTS that consequently affect the blood pressure (BP) and heart rate (HR). The following two figures are selected from the original article. Figure 1A showed microinjection of adenosine in NTS can slowly induce decreases in both blood pressure (BP) and heart rate (HR) that can be blocked by specific MEK inhibitor PD98059 that indicated the ERK is a downstream signal molecule in  Adenosine mediated cardiovascular regulatory effects. The similar result was shown in Figure 1B and indicated that eNOS a downstream signal molecule in Adenosine mediated cardiovascular effects. We also demonstrated the ERK can phosphorylate and activate eNOS and regulated NO production in NTS (figure 5 in the article). Figure 2A and 2B showed the results of western blot and immunohistochemistry that ERK-eNOS signaling indeed was activated in NTS upon adenosine stimulation.
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