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Neuromodulation in Treatment of Hypertension by Acupuncture: a Neurophysiological Prospective

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Neuromodulation in Treatment of Hypertension by Acupuncture: a Neurophysiological Prospective Vol.5, No.4A, 65-72 (2013) Health http://dx.doi.org/10.4236/health.2013.54A009 Neuromodulation in treatment of hypertension by acupuncture: A neurophysiological prospective Peyman Benharash1, Wei Zhou2* 1Division of Cardiothoracic Surgery, University of California, Los Angeles, USA 2Department of Anesthesiology, University of California, Los Angeles, USA; *Corresponding Author: [email protected] Received 28 February 2013; revised 30 March 2013; accepted 6 April 2013 Copyright © 2013 Peyman Benharash, Wei Zhou. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT study the effects of acupuncture on the hyper- tensive man. Hypertension is a major public health problem affecting over one billion individuals worldwide. Keywords: Central Nervous System; This disease is the result of complex interac- Electroacupuncture; Neurotransmitter; Brain Stem tions between genetic and life-style factors and the central nervous system. Sympathetic hyper- activity has been postulated to be present in 1. INTRODUCTION most forms of hypertension. Pharmaceutical Hypertension has become a serious public health prob- therapy for hypertension has not been perfected, lem impacting over one billion lives worldwide [1]. At often requires a multidrug regimen, and is as- the turn of this century, 7.6 million deaths were attribut- sociated with adverse side effects. Acupuncture, able to hypertension. The majority of this disease burden a form of somatic afferent nerve stimulation has occurred in working people in low to middle-income been used to treat a host of cardiovascular dis- countries, while its prevalence increases with age and the eases such as hypertension. It has long been lifetime risk of developing hypertension approaches 90% established that the two major contributors to [2]. With the growing elderly population, dietary and systemic hypertension are the intrarenal renin- life-style changes, the incidence of hypertension is ex- angiotensin system and chronic activation of pected to continue to increase. the sympathetic nervous system. A number of There exist complex physiologic interactions between important studies on the baroreflex response multiple organ systems that lead to hypertension. Genetic and its response to acupuncture are discussed. and environmental factors play a large role in develop- The inhibitory effects of acupuncture on the ros- tral ventrolateral medulla (rVLM) reduces sym- ment of this disease. Such intricacies have led clinicians pathetic nerve activity and blood pressure sug- to evaluate the efficacy of a wide range of therapeutics. gesting overactivity of the angiotensin system in Current pharmacologic approaches to hypertension in- this nucleus may play a role in the maintenance clude agents that affect myocardial contractility and of hypertension. Our experimental studies have chronotropy, vascular tone, salt and water retention. All shown that electroacupuncture stimulation ac- of these pharmaceuticals have numerous side effects, are tivates neurons in the arcuate nucleus, ventro- costly and are often only partially effective requiring lateral gray, and nucleus raphe to inhibit the treatment with multidrug regimens. neural activity in the rVLM in a model of visceral Experimental evidence suggests that hyperactivity of reflex stimulation-induced hypertension. The sig- the central nervous system may be involved in the patho- nificant role of spinal cord opioids and nociceptin genesis of hypertension. For instance, individuals with are also reviewed. Although clinical studies of high sodium intake and reduced natruresis due to high acupuncture to date have met some success, levels of renin release are prone to developing high blood they are rarely scientifically robust and do not pressure. The activity of the sympathetic nervous system feature randomization and long-term follow up. (SNA) contributes to renin release which in turn leads to Based on a great deal of basic scientific evi- increased vascular tone as well as salt retention by in- dence, large trials are desperately needed to creasing the levels of angiotensin and aldosterone. Copyright © 2013 SciRes. OPEN ACCESS 66 P. Benharash, W. Zhou / Health 5 (2013) 65-72 Acupuncture, a form of somatic afferent nerve stimu- rial baroreflexes [5,7-9]. lation, has long been postulated to exert its effects through Functional changes have been detected largely in hy- the nervous system. Manual acupuncture and its potent pothalamic and medullary areas that modulate sympa- alternative, electroacupuncture (EA), have been used in thetic outflow [10]. Ang II contributes to cardiovascular Asian counties to treat many cardiovascular disorders. regulation via its direct action at various hypothalamic Many physicians, however, are reluctant to use acupunc- and medullary areas to enhance sympathetic outflow, ture due to its controversial benefits and largely unknown blunt the sensitivity of the baroreflex, and stimulate se- physiological mechanisms of action. cretion of vasopressin [11,12]. In this paper, the current body of knowledge on the effects of acupuncture on the cardiovascular system will 3. CENTRAL MECHANISM OF be reviewed. We will describe the central nervous mecha- ACUPUNCTURE nisms of acupuncture and provide the rationale for the Over the past decade, our group and others have sys- use of this technique in the treatment of hypertension. tematically examined the central neural regulation of 2. CENTRAL REGULATION OF BLOOD visceral reflex-induced hypertension by acupuncture in different regions of brain and spinal cord. A brief de- PRESSURE scription of our findings using EA will be described in There is clear scientific evidence supporting the criti- the ensuing sections. cal role of the central nervous system in the development and maintenance of hypertension. In particular, increases 3.1. EA Inhibition of Neural Activity in the in SNA and derangements in arterial baroreflex function rVLM appear to contribute to the pathogenesis of this disease The rVLM plays a critical role in the regulation of BP [3]. Development of hypertension in various animal mod- [13], while inhibition of neuronal function in this region els of hypertension, such as the spontaneously hyperten- results in a large drop in BP [14]. We have demonstrated sive rat (SHR), the renin transgenic (TGR mRen2) rat, that both low frequency electro- and manual-acupuncture the Dahl salt-sensitive rat and the dexycorticosterone inhibit premotor sympathetic neural firing in the rVLM acetate (DOCA)-salt rat, is associated with increased in and lower BP [15]. Administration of naloxone (non- sympathetic nerve firing. The effector mechanisms for specific opioid receptor antagonist) or gabazine (γ-ami- hypertension through increased sympathetic activity in- nobutyric acid or GABA type A receptor blocker) in the clude increase in vascular tone, as well as enhancement rVLM abolishes the EA effect, implicating the opioid of the chronotropic and inotropic properties of the heart. receptors in this response [16]. The rVLM is an impor- The end result of such alterations is a higher than normal tant brain stem region that processes somatic inputs dur- cardiac output and peripheral vascular resistance. ing acupuncture stimulation. Electrophysiological studies The effects of SNA on the kidneys have been eluci- of neuronal activity in the rVLM have shown that, as dated and recently garnered particular clinical and thera- compared to cardiovascular inactive points (LI 6-7, G peutic attention. Sympathetic activation stimulates renin 37-39), P 5-6 and certain acupoints along the large intes- secretion that in turn activates the renin-angiotensin-al- tine meridian (LI 4-11), located over deep somatic neural dosternone system leading to angiotensin (Ang) II-in- pathways (median and deep radial nerves), provide more duced vasoconstriction and sodium retention [4]. This afferent input to cardiovascular premotor sympathetic feature leads to increased preload and therefore high car- neurons in the rVLM [17]. This observation likely ex- diac-output hypertension. plains why acupuncture over these deep nerves most ef- Alteration of arterial baroreflex function has also been fectively lower elevated sympathetic outflow and BP. implicated in the development of hypertension [5]. Ca- rotid sinus and aortic arch baroreceptors respond to changes 3.2. Neurotransmitters in rVLM, ARC, and in blood pressure (BP) by modulating parasysmpathetic vlPAG and sympathetic outflow, thus controlling heart rate car- diac output and vasomotor tone. In response to a persis- Investigations of EA in several early models of hyper- tent elevation of BP, the baroreflex resets towards a tensions suggested that release of opioids, GABA, no- higher pressure setpoint [6]. Under hypertensive condi- ciceptin and serotonin in the rVLM are responsible for tions, resetting of the operational point of the arterial the BP-lowering effects of acupuncture [18-22]. More baroreflex therefore contributes to maintaining a high BP recently, we have demonstrated that the EA inhibition of rather than opposing it. Similar to animal models of hy- visceral reflex-induced hypertension in the cat is related pertension, hypertension in human subjects is associated to the activation of µ- and δ-, but not қ-opioid receptors with increases in sympathetic activity and blunted arte- in the rVLM. Based on these observations,
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