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Effect and Mechanism of Acupuncture on Hypertension

Approximately 25% of the adult population in the UK have hypertension (i.e. a blood pressure of 140/90mmHg or more), and over half of those over the age of 60s are affected according to the report published by National Clinical Guideline Centre in 2011. In the United States the prevalence was 29% between 2011 and 2014. China likewise has a high prevalence of hypertension as noted in a cross-sectional study between 2007–2008 (29% vs 24% males vs females) (Longhurst et al., 2017). The prevalence is strongly influenced by age and lifestyle factors. Raised systolic pressure is the more dominant feature of hypertension in older patients, while raised diastolic pressure is more common in younger patients (i.e. those under 50 years of age).

High blood pressure can be lowered by several classes of drugs and by such lifestyle changes as salt intake restriction, exercise and weight loss. Lifestyle interventions, however, are difficult to achieve and even more difficult to maintain. Drug therapy is costly, fraught with compliance, and accompanied by side effects. Hence, there is a rational for consideration of additional effective therapies, such as acupuncture.

There have been accumulated reports on the basic studies and clinical investigations regarding to acupuncture treatment for hypertension during past decades, which has significantly enhanced our understanding about underlying effect of acupuncture as a modality on the regulation of blood pressure. Here is a brief review of some recent development in acupuncture treatment of hypertension.

 

Mechanisms of acupuncture reducing hypertension

Recently, the mechanism underlying effect of acupuncture on blood pressure regulation has been extensively studied. Li and colleagues (2016) investigated the action mechanism of electroacupuncture in lowing blood pressure in hypertension model. Electroacupuncture was applied at ST36-37 acupoints overlying the deep peroneal nerve for 30 min twice a week for five weeks. Elevated blood pressure was markedly reduced after six sessions of treatments and remained low 72 hrs after treatment compared with control groups. Biochemical studies found that mRNA level of preproenkephalin in the brain area called rostral ventrolateral medulla was significantly increased in those electroacupuncture-treated hypertension model. Further, microinjection of ICI 174,864, a δ-opioid receptor antagonist, into the rVLM of electroacupuncture-treated hypertension model partially reversed effect of electroacupuncture on increased blood pressure. The results showed that electroacupuncture-induced increase in mRNA level of preproenkephalin in the rostral ventrolateral medulla is closely associated with significantly decreased blood pressure.

 

Renal sympathetic nervous system regulates blood pressure via epinephrine and norepinephrine which modulates expression of beta-adrenergic receptors (beta-ARs). Of the two main beta-AR subtypes, beta1-AR signalling has been linked to cardiotoxicity and beta2-AR activates signalling pathways of cardioprotection. Recently a study was conducted to examine the effect of acupuncture on activation of the renal sympathetic nervous system and expression of beta-AR subtypes in spontaneous hypertensive rat (SHRs) rat model (Yang et al., 2017). It was found that acupuncture at LR3 reduced mean blood pressure and regulated hear rate availability in the model. The therapeutic effects of acupuncture were closely associated with the significant reductions in the plasma levels of epinephrine and norepinephrine and the content of renin (Yang et al., 2017). In addition, acupuncture decreased beta1-AR expression and increased beta2-AR expression, indicating acupuncture has bidirectional regulation effects on beta-ARs (Yang et al., 2017).

Effect of electroacupuncture at PC6 on the hypertension and myocardial hypertrophy in SHRs model was conducted (Xin et al. 2017). After electroacupuncture treatment once a day in 8 consecutive weeks, the enhanced BP in SHR + EA group was significantly lower compared to control group. Echocardiographic, morphological studies showed that the enhanced left ventricular anterior and posterior wall end-diastolic thickness, diameters and cross-sectional area of cardiac myocyte, as well as the ratio of heart weight to body weight, were markedly diminished in acupuncture group compared with control groups. Electroacupuncture stimulation significantly attenuated the levels of Angiotensin-converting enzyme and Angiotensin II Type 1 and 2 receptors (AT1R, AT2R) in SHRs compared with control (Xin et al., 2017). The results suggest that electroacupuncture stimulation at bilateral PC6 could arrest the hypertension development and ameliorate the cardiac hypertrophy and malfunction in SHRs, which might be mediated by the regulation of ACE, AT1R, and AT2R.

Further model studies reported that neuronal pathways, circuitry and synaptic transmission involved in electroacupuncture’s cardiovascular responses at acupoints P5-P6 and ST36-ST37 on sympathoexcitatory reflex responses elicited by activation of visceral afferents in cats and rats (see review Longhurst & Tjen-A-Looi, 2017). For example, spinal visceral afferent pathways ascending to medulla, midbrain and hypothalamus activate cardiovascular neurons, which can be modifed by 30 min electroacupuncture stimulation at P5-P6 through activating median nerves and ST36-ST37 through activating deep peroneal nerves to reduce sympathetic outflow that in turn influences cardiovascular function. Acupuncture also manipulates the activities of neurons that regulate cardiovascular function in the paraventricular nucleus (PVN), arcuate nucleus (ARC), ventrolateral periaqueductal gray(vlPAG), nucleus raphe-pallidus (NR-P), rostral ventrolateral medullar (rVLM) (see review Longhurst & Tjen-A-Looi, 2017). Acupuncture also induce regulation of release of neurotransmitters beta-endorphin (β-End), acetylcholine (ACh), L-glutamate (L-Glu), gamma-butyric acid (GABA), enkephalin (Enk), serotonin 1A receptor (5-HT1A) that participate in the central neural processing during electroacupuncture stimulation (see review Longhurst & Tjen-A-Looi, 2017).

 

What is optimal stimulation frequency of electroacupuncture to decrease blood pressure in human?

Electroacupuncture is used to treat patient with hypertension, because it is less dependent on practioner’s skill, and the frequency and duration of stimulation can be precisely controlled. However, there is no study in human subject about the optimal stimulation frequency in reducing blood pressure.

Nakahara et al., (2016) conducted a clinical study to investigate the effects of varying stimulation frequencies of electroacupuncture on time-dependent changes in blood pressure and heart rate in humans. Twenty healthy human subjects were recruited for the study. Electroacupuncture was performed at acupoint Ximen (PC4) for 6 mins, at an intensity of 1 V, pulse width of 5 ms, using following stimulation frequencies: 0.5, 1, 5 and 10 HZ. The beginning of electroacupuncture was blinded to subject. Blood pressure and heart rate were monitored two mins before acupuncture and during 6 mins electroacupuncture stimulation. 

The data showed that electroacupuncture stimulation at 1 HZ produced the maximal reduction in blood pressure and heart rate compared with other stimulation frequencies. Further, reduction effect became more pronounced with increase in stimulation duration. The study provided fundamental data for potential use of electroacupuncture in the treatment of cardiovascular conditions.

 

How does acupuncture exert long-lasting reduction of blood pressure in patients with hypertension?

Li et al., (2015) carried out a randomized controlled clinical trial to assess the effectiveness and underlying mechanism of eletroacupuncture on hypertension. Sixty-five patients with mild to moderate hypertension, not receiving any medication, were randomly divided into treatment group (n=33) and control group (n=32). Patients in treatment group were given electroacupuncture at acupoints PC5-6+ST36-37, which are thought to have anti-hypertensive effects, for 30min, once a week for 8 weeks. Patients in control group were given electroacupuncture at acupoints LI6-7+GB37-39 which are thought to be irrelevant to blood pressure. Patients were assessed with 24-hour ambulatory blood pressure monitoring to measure the peak and average systolic BP and diabolic BP. Biochemical studies undertaken to look the changes in plasma levels of norepinephrine, renin and aldosterone before and after 8-week treatment.

At the end of 8-week treatment, patients in treatment group had a significant decrease in systolic BP and diabolic BP compared with control group. Four-week follow up found that long-lasting blood pressure-lowering acupuncture effect was still observed in 14 of 33 patients in treatment group. Biochemical studies showed plasma level of norepinephrine, renin and aldosterone, which were initially elevated, was reduced by 41%, 67% and 21% respectively in those patients.

The study showed that electroacupuncture at specific acupoints alone was able to reduced both systolic BP and diabolic BP. Modulation of renin-aldosterone and sympathetic systems were likely linked to long-lasting actions of electroacupuncture. However, further studies with large sample size are needed to confirm the results.

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