Acupuncture and its potent alternative, electroacupuncture (EA), are accepted treatments for pain, nausea and vomiting. Small trails further suggest that EA can lower elevated blood pressure. Studies conducted in the last two grant cycles have evaluated supra-spinal mechanisms underlying EA's ability to reduce elevated sympathetic outflow and blood pressure. Acupuncture is differentiated from non-specific somatosympathetic stimulation by its relative point specificity and its prolonged action. We recently demonstrated point specific blood pressure modulation with the largest effect occurring during low frequency, low intensity EA at the pericardial and stomach meridians, specifically at P5-P6 and St36-St37, since these sets of acupoints provide significant input to premotor sympathetic neurons in the rostral ventrolateral medulla (rVLM). We also have demonstrated that opioids, specifically endorphins and enkephalin, nociceptin and (-amino butyric acid (GABA), mediate the initial EA-related inhibition while opioids and GABA underlie prolonged modulation of blood pressure by EA. EA works both pre- and post- synaptically on rVLM glutamate release, to lower sympathetic outflow. This renewal extends our studies to investigate EA segmental regulation of elevated blood pressure through actions involving dynorphin and nociceptin in the spinal cord dorsal horn and intermediolateral columns. In addition, we recently have begun to explore the potential for acupuncture to elevate depressed blood pressure in two models of reflex vasodepression. The first uses phenylbiguanide (PBG) in chloralose anesthetized cats to stimulate 5- hydroxytryptamine-3 (5-HT3) cardiopulmonary receptors to reflexly lower heart rate and blood pressure through pathways in the medial nucleus tractus solitarii (mNTS) and nucleus ambiguus (NA). The second involves reflex cardiovascular depression during mild gastric distension in ketamine-xylazine anesthetized rats, which appears to inhibit the prevagal neurons in the NA and presympathetic neurons in the rVLM through a GABAA mechanism, likely originating from the caudal ventrolateral medulla (cVLM). Preliminary data suggest that EA modulates these cardiodepressor reflexes through GABAergic, 5-HT or opioidergic mechanisms in the mNTS, nucleus raphe pallidus and NA during PBG stimulation and through GABA in the cVLM and NA during gastric distension. Additional studies, which have important clinical implications, will investigate stimulation modality and the underlying mechanisms, including point specificity, frequency modulation and spatial summation by combining two sets of acupoints. An improved understanding of acupuncture's ability to normalize blood pressure through its spinal and supraspinal actions, as well as underlying mechanisms, will provide important clues that can assist in the clinical use of acupuncture in conditions of either elevated or depressed blood pressure and will contribute to increased acceptance of this therapeutic technique by the western medical and scientific communities.

Public Health Relevance

Project Narrative Blood pressure abnormalities are major risk factors for coronary artery disease, stroke, congestive heart failure and syncope. However, both hypertension and hypotension are poorly treated because many patients often are unwilling to use standard medical therapy. Today in the US, patients increasingly are looking for integrative therapies that are more acceptable for treatment of their blood pressure abnormality. Although acupuncture may be a viable inexpensive alternative that has a very low incidence of side effects, physicians generally are reluctant to recommend this therapy because little data are available on its efficacy and particularly on its mechanisms of action. The current application will provide important new information on both efficacy and mechanism of action in acupuncture treatment of either elevated or low blood pressure.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL063313-12
Application #
8208060
Study Section
Special Emphasis Panel (ZRG1-CVS-B (02))
Program Officer
Maric-Bilkan, Christine
Project Start
2000-09-20
Project End
2013-12-31
Budget Start
2012-01-01
Budget End
2012-12-31
Support Year
12
Fiscal Year
2012
Total Cost
$378,675
Indirect Cost
$131,175
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
Longhurst, John C; Tjen-A-Looi, Stephanie (2013) Acupuncture regulation of blood pressure: two decades of research. Int Rev Neurobiol 111:257-71
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, Peng; Tjen-A-Looi, Stephanie C (2013) Mechanism of the inhibitory effect of electroacupuncture on experimental arrhythmias. J Acupunct Meridian Stud 6:69-81
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
Tjen-A-Looi, Stephanie C; Li, Peng; Li, Min et al. (2012) Modulation of cardiopulmonary depressor reflex in nucleus ambiguus by electroacupuncture: roles of opioids and ?-aminobutyric acid. Am J Physiol Regul Integr Comp Physiol 302:R833-44
Guo, Zhi-Ling; Li, Min; Longhurst, John C (2012) Nucleus ambiguus cholinergic neurons activated by acupuncture: relation to enkephalin. Brain Res 1442:25-35
Tjen-A-Looi, Stephanie C; Hsiao, An-Fu; Longhurst, John C (2011) Central and peripheral mechanisms underlying gastric distention inhibitory reflex responses in hypercapnic-acidotic rats. Am J Physiol Heart Circ Physiol 300:H1003-12
Guo, Zhi-Ling; Longhurst, John C (2010) Activation of reciprocal pathways between arcuate nucleus and ventrolateral periaqueductal gray during electroacupuncture: involvement of VGLUT3. Brain Res 1360:77-88
Moazzami, Ali; Tjen-A-Looi, Stephanie C; Guo, Zhi-Ling et al. (2010) Serotonergic projection from nucleus raphe pallidus to rostral ventrolateral medulla modulates cardiovascular reflex responses during acupuncture. J Appl Physiol 108:1336-46
Li, Peng; Longhurst, John C (2010) Neural mechanism of electroacupuncture's hypotensive effects. Auton Neurosci 157:24-30

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