The use of acupuncture has increased markedly in the US over the last three decades. Although NCCAM is sponsoring clinical trials on acupuncture in cardiovascular disease, including hypertension, coronary artery disease or arrhythmias, the mechanisms underlying its influence are poorly understood. We have shown that electro acupuncture (EA) at the Neiguan acupoint over the median nerve reduces sympathoexcitatorycardiovascular reflex responses. Through an opioid mechanism, involving mu and delta receptors in the rostral ventrolateral medulla (rVLM), EA inhibits premotor sympathoexcitatory neurons that receive convergent input from the median and splanchnic (gallbladder) nerves. However, a long loop reflex likely exists involving the arcuate nucleus (ARC) and the caudal ventrolateral periaqueductal gray (PAG), in addition to the rVLM in the EA response. Preliminary anatomical and electrophysiological data suggest that these regions play a role in EA-cardiovascular response. The present proposal will use a combined neuroanatomical, electrophysiological and pharmacological approach to evaluate the role of the ARC and PAG in this response through three hypotheses. First, stimulation of the Neiguan acupoint increases c-Fos immunoreactivity in the ARC, PAG and rVLM whereas stimulation of the gallbladder increases c-Fos expression only in the PAG and rVLM. Cells in these regions will either be co-labeled or in close proximity to neurons or axons containing immunoreactive beta-endorphin or met-enkephalin. Second, EA increases activity in neurons of the ARC, which project to the PAG and through an opioid mechanism facilitates visceral somatic convergent inhibition in the PAG. Third, neurons in the PAG receiving convergent inhibition from the median and splanchnic nerves project to the rVLM where they inhibit evoked activity in sympathetic premotor neurons and the resulting cardiovascular responses. Understanding the pathways and the central neural integration by which EA at the Neiguan acupoint inhibits reflex excitatory cardiovascular responses will provide a greater understanding of the mechanisms underlying the beneficial modulation of the cardiovascular system by this alternative therapy. Such knowledge, along with the current clinical trials, will encourage acceptance of this therapy by scientists and clinicians in the US and other Western countries.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL072125-03
Application #
6894633
Study Section
Special Emphasis Panel (ZRG1-ECS (02))
Program Officer
Lin, Michael
Project Start
2003-07-01
Project End
2007-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
3
Fiscal Year
2005
Total Cost
$379,792
Indirect Cost
Name
University of California Irvine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Guo, Zhi-Ling; Fu, Liang-Wu; Su, Hou-Fen et al. (2018) Role of TRPV1 in acupuncture modulation of reflex excitatory cardiovascular responses. Am J Physiol Regul Integr Comp Physiol 314:R655-R666
Tjen-A-Looi, Stephanie C; Fu, Liang-Wu; Guo, Zhi-Ling et al. (2018) Modulation of Neurally Mediated Vasodepression and Bradycardia by Electroacupuncture through Opioids in Nucleus Tractus Solitarius. Sci Rep 8:1900
Longhurst, John C; Tjen-A-Looi, Stephanie C (2017) Evidence-based blood pressure reducing actions of electroacupuncture: mechanisms and clinical application. Sheng Li Xue Bao 69:587-597
Li, Min; Tjen-A-Looi, Stephanie C; Guo, Zhi-Ling et al. (2016) Repetitive Electroacupuncture Attenuates Cold-Induced Hypertension through Enkephalin in the Rostral Ventral Lateral Medulla. Sci Rep 6:35791
Tjen-A-Looi, Stephanie C; Guo, Zhi-Ling; Fu, Liang-Wu et al. (2016) Paraventricular Nucleus Modulates Excitatory Cardiovascular Reflexes during Electroacupuncture. Sci Rep 6:25910
Cheng, Ling; Li, Peng; Tjen-A-Looi, Stephanie Cheeyee et al. (2015) What do we understand from clinical and mechanistic studies on acupuncture treatment for hypertension? Chin Med 10:36
Tjen-A-Looi, Stephanie C; Guo, Zhi-Ling; Longhurst, John C (2014) GABA in nucleus tractus solitarius participates in electroacupuncture modulation of cardiopulmonary bradycardia reflex. Am J Physiol Regul Integr Comp Physiol 307:R1313-23
Tjen-A-Looi, Stephanie C; Guo, Zhi-Ling; Li, Min et al. (2013) Medullary GABAergic mechanisms contribute to electroacupuncture modulation of cardiovascular depressor responses during gastric distention in rats. Am J Physiol Regul Integr Comp Physiol 304:R321-32
Li, Min; Tjen-A-Looi, Stephanie C; Guo, Zhi-Ling et al. (2013) Electroacupuncture modulation of reflex hypertension in rats: role of cholecystokinin octapeptide. Am J Physiol Regul Integr Comp Physiol 305:R404-13
Longhurst, John C; Tjen-A-Looi, Stephanie (2013) Acupuncture regulation of blood pressure: two decades of research. Int Rev Neurobiol 111:257-71

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