Acupuncture Combats Hypertension in University of California Research

A team of University of California (Irvine) researchers conclude that acupuncture is effective for the treatment of high blood pressure. In a controlled laboratory study, the team not only documented the efficacy of acupuncture but also demonstrated the mechanisms of effective action. The University of California team has proven that electroacupuncture (the stimulation of a filiform needle with electricity) at acupuncture point ST36 (Zusanli) promotes enkephalin production that dampens proinflammatory excitatory responses from the sympathetic nervous system that are responsible for hypertension. The researchers note that electroacupuncture regulates chemical changes to the area of the brain responsible for nervous system responses that control cardiovascular function.

The researchers document that electroacupuncture achieves this result by directly influencing preproenkephalin (PPE) gene expression. PPE is a precursor substance that encodes proenkephalin, which then stimulates the production of enkephalin (an endogenous opioid with powerful pain killing actions). The research documents that electroacupuncture reduces blood pressure through the regulation of this process. 

Previous studies demonstrate the efficacy of acupuncture for the treatment of hypertension. [1] The University of California study confirms the prior research and also documents the mechanisms of effective action. The research team used opioid receptor antagonists to confirm that electroacupuncture’s ability to regulate enkephalin caused the lowering of hypertension. We’ll take a look at how they double-checked their work later in this article.

The laboratory study was conducted on rats with cold-induced hypertension (CIH). The University of California researchers demonstrate that electroacupuncture attenuates cold-induced hypertension. Electroacupuncture lowers both systolic and diastolic blood pressure and the physiological response remains for at least 72 hours after repeated treatments. Thus, this study not only demonstrates but proves that acupuncture can be effectively used for the treatment of hypertension.

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Hypertension poses an enormous public health risk worldwide. Hypertension dramatically increases the risk of stroke, heart attack, and heart failure. Additionally, it is second only to diabetes as an antecedent to end stage renal disease. [2] In the year 2000, over 26% of the adult population had hypertension, enumerating approximately 972 million people globally, and those numbers are expected to rise. [3] In 2010 in the United States alone, over 1 million people died from cardiovascular, lung, and blood diseases, accounting for 41% of all deaths. Among these, the leading cause of death is heart disease and cerebrovascular disease (including stroke) ranks fourth. [4] In the United States, the estimated cost of treating these illnesses in 2009 accounted for $424 billion, or 23% of costs associated with illness and death. [5]

The effective treatment of hypertension could save millions of lives by preventing the sequelae associated with high rates of morbidity. It could also dramatically decrease the cost of healthcare worldwide, by millions if not billions of dollars annually. Based on the evidence, electroacupuncture is an important treatment option and must be seriously considered for its potential in both these realms: clinical efficaciousness and cost-effectiveness.

The researchers chose to induce hypertension with cold temperatures because CIH “is as or more clinically relevant than elevation of BP in other hypertensive models.” [6] Most forms of induced hypertension require surgery or high doses of drugs or hormones, which might affect the accuracy of the results. [7] Alternatively, CIH is a “‘naturally-occurring’ form of hypertension, associated with chronic cold-induced stress that is a common cause for essential hypertension.” [8] Within 4 weeks of exposure to temperatures of 6°C (42.8°F), the rats developed sustained CIH. The mechanism of CIH is similar to essential hypertension in humans and thus the outcomes of the study will presumably correspond more closely with, and the treatment will be more applicable to, patients with essential hypertension. More specifically, CIH stimulates the sympathetic nervous system.

The sympathetic and parasympathetic nervous systems are the two branches of the autonomic nervous system. The autonomic nervous system controls the internal organs, and is responsible for most unconscious or automatic actions, including digestion, respiration, and cardiac regulation. The parasympathetic system has more influence over restful activities such as digestion, while the sympathetic nervous system is more excitatory; it is often designated as the ‘fight or flight’ system because of its role in responding to external stresses. Among other roles, this includes the short-term regulation of blood pressure.

When the body is under stress, including extended exposure to cold, the sympathetic nervous system increases blood pressure in an attempt to maintain body temperature and proper blood flow, thus causing CIH. Like other parts of the nervous system, the activity of the sympathetic nervous system is controlled by neurotransmitters (endogenous chemical messengers including peptides) that interact with ‘receptors’ to determine whether a neuron will activate (excitatory) or remain at rest (inhibitory). In this study, researchers tested levels of PPE gene expression to determine the presence of enkephalin, an opiate-like neuropeptide that has an inhibitory effect on sympathetic activity. Through PPE gene expression, if the sympathetic system increases blood pressure in response to stress, enkephalins would dampen this effect by interacting with δ-opioid receptors thereby lowering blood pressure. [9]

The researchers used a series of tests to determine the effects that CIH has on the chemicals present in the rostral ventrolateral medulla (the area of the brain associated with the sympathetic reflexes that control cardiovascular function) as well as the effect of electroacupuncture on these chemicals. They studied the rats in 4 groups: normotensive with no acupuncture, CIH alone, CIH with sham-electroacupuncture, and CIH with true electroacupuncture at ST36. By dissecting the brains 72 hours after the course of treatments ended, they were able to precisely test the levels of the chemicals still present in the rostral ventrolateral medulla (rVLM), demonstrating the extended efficacy of the treatments. Their results are thorough, addressing both the mechanism of action and the effect of electroacupuncture on hypertension.

By injecting normotensive rats with either a δ-opioid agonist (DADLE) to excite the receptor or a δ-opioid receptor antagonist (ICI 174,864) to inhibit a response. They demonstrated that interaction with the δ-opioid receptors in normotensive rats had no effect on blood pressure. The lack of change with either the δ-opioid agonist or antagonist shows that sympathoexcitation is limited to conditions of stress. Some rats in the sham-electroacupuncture test group were injected with the δ-opioid agonist; the hypotensive effect seen in these rats mimicked the effect of electroacupuncture. This suggests that the δ-opioid system participates in the hypotensive action witnessed in the electroacupuncture test group.

Among the electroacupuncture test group, the rats showed a dramatic increase in PPE in the rVLM compared to all three other test groups, [10] as well as a decrease in both systolic and diastolic blood pressure not seen in the others. [11] In order to ensure that this was indeed related to the decrease in blood pressure, two members of this group were given naloxone, a non-specific opioid receptor antagonist. Both experienced a subsequent elevation in blood pressure, demonstrating with even more precision that it is indeed enkephalins interacting with δ-opioid receptors that are the mechanism of action for the decrease in blood pressure in rats with sustained blood pressure elevation due to CIH. [12]

This research provides us with concrete evidence that repeated treatments with electroacupuncture reduces sustained hypertension and indicates that these treatments have an extended hemodynamic action. The National Institutes of Health (NIH) has asserted in its own studies that the activation of δ-opioid receptors “reduces persistent pain and improves negative emotional states.” [13] The University of California research concludes that electroacupuncture regulates enkephalins interacting with δ-opioid receptors. As a result, the treatment of hypertension and other clinical scenarios involving regulation δ-opioid receptors are indicated.

Notes
1. Cevic, C and Iseri, SO. The effect of acupuncture on high blood pressure of patients using antihypertensive drugs. Acupuncture & electro-therapeutics research 2013; 38(1-2): 1-15. ncbi.nlm.nih.gov/pubmed/23724695
2. Chobanian, AV et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003: 289(19): 2560-72. nhlbi.nih.gov/files/docs/guidelines/jnc7full.pdf (pg 6)
3. Kearney, Patricia M et al. Global burden of hypertension: analysis of worldwide data. Lancet 2005; 365(9455): 217 -- 223 thelancet.com/journals/lancet/article/PIIS0140-6736(05)17741-1/abstract
4. nhlbi.nih.gov/about/documents/factbook/2012/chapter4
5. nhlbi.nih.gov/about/documents/factbook/2012/chapter4
6. Li, Min et al. Repetitive Electroacupuncture Attenuates Cold-Induced Hypertension through Enkephalin in the Rostral Ventral Lateral Medulla. Scientific Reports 2016; 6(35791): 2 nature.com/articles/srep35791
7. Li, Min et al. Repetitive Electroacupuncture: 2
8. Li, Min et al. Repetitive Electroacupuncture:1--2
9. pubchem.ncbi.nlm.nih.gov/compound/461776#section=Pharmacology-and-Biochemistry
10. Li, Min et al. Repetitive Electroacupuncture:4
11. Li, Min et al. Repetitive Electroacupuncture:3
12. Li, Min et al. Repetitive Electroacupuncture:2
13. Pradhan, Amynah A et al. The delta opioid receptor: an evolving target for the treatment of brain disorders. Trends in Pharmacological Sciences 2012; 32(10): 581--590. ncbi.nlm.nih.gov/pmc/articles/PMC3197801/

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