Neuroendocrine Mechanisms of Acupuncture in the Treatment of Hypertension

Arterial hypertension affects approximately 1 billion people worldwide, representing one of the most prevalent chronic disorders. Although there are several pharmacologic strategies for its treatment, they frequently present adverse side effects and have not been perfectly developed. In this context, acupuncture emerges as a promising complementary therapy for the treatment of cardiovascular diseases, including hypertension. This comprehensive review examines the neuroendocrine mechanisms by which acupuncture exerts its antihypertensive effects, providing a robust scientific perspective on this ancient therapeutic technique.

Experimental studies demonstrate that electroacupuncture (EA) inhibits hypertension induced by visceral reflexes through modulation of the activity of cardiovascular presympathetic neurons in the rostral ventrolateral medulla (rVLM). The mechanism involves the activation of neurons in the arcuate nucleus of the hypothalamus, in the ventrolateral periaqueductal gray (vlPAG) of the midbrain, and in the nucleus raphe pallidus (NRP) of the medulla. These neural circuits work together to inhibit the activity of sympathetic premotor neurons in the rVLM. The specificity of acupuncture points is fundamental to treatment efficacy.

Points PC-5–PC-6 (pericardium meridian, over the median nerve) and LI-10–LI-11 (large intestine meridian, over the deep radial nerve) have demonstrated greater efficacy in reducing reflex hypertension. Direct stimulation of the nerves underlying the acupoints produces similar results, suggesting that activation of specific neural pathways is crucial for the cardiovascular effects of acupuncture. Stimulation parameters are critical for therapeutic success. Low-frequency electroacupuncture (2 Hz) with low current (2 mA) for 30 minutes has been shown to be more effective than higher frequencies (40-100 Hz).

This frequency specificity is related to the differential release of neuropeptides: 2 Hz significantly increases enkephalin-like immunoreactivity, while 100 Hz increases dynorphin immunoreactivity. Analysis of the neurotransmitters involved reveals a complex modulatory system. In the rVLM, opioids (particularly enkephalins and β-endorphins), GABA, nociceptin, and serotonin participate in the antihypertensive response to electroacupuncture. The administration of naloxone (a nonspecific opioid antagonist) or gabazine (a GABA type A receptor blocker) in the rVLM abolishes modulation by EA, confirming the role of these neurotransmitter systems.

The long-loop circuit for cardiovascular modulation by EA involves excitatory projections from the arcuate nucleus to the vlPAG, which are essential for the inhibitory influence of EA on reflex hypertension. The vlPAG, in turn, provides inhibitory input to sympathetic premotor neurons in the rVLM through direct and indirect connections via the nucleus raphe pallidus. This indirect pathway uses serotonergic projections that act on 5-HT1A receptors in the rVLM. The effects of acupuncture extend beyond the central nervous system, also influencing the endocrine system.

Studies demonstrate reductions in plasma levels of renin, aldosterone, angiotensin II, and norepinephrine, reflecting acupuncture's ability to modulate the neurohormonal system. Additionally, acupuncture increases the expression of neuronal nitric oxide synthase in brainstem nuclei, contributing to central cardiovascular regulation. The temporal aspect of acupuncture effects presents unique characteristics. There is a short-term immediate post-stimulation effect, with significant reductions in diastolic blood pressure immediately after 30 minutes of acupuncture.

More importantly, preliminary studies with 24-hour ambulatory monitoring have demonstrated that 8 weeks of acupuncture reduce the blood pressure of hypertensive patients by 12-18 mmHg, with effects persisting for 4 weeks after the end of treatment. The mechanisms of prolonged action may involve reinforcement circuits between the arcuate nucleus and the vlPAG, activated by extended periods of EA (30-60 minutes). Preliminary data using real-time PCR demonstrate that preproenkephalin in the rVLM increases after a single 30-minute EA application, suggesting that EA may exert lasting effects by stimulating increased production of opioid precursors. The spinal cord also plays an important role in the processing of acupuncture cardiovascular responses.

The dorsal horn serves as the principal center for EA-induced analgesia, and studies show that both opioids and nociceptin at the spinal level can regulate sympathetic outflow through modulation of transmission between the brainstem and the intermediolateral column. Despite significant advances in the understanding of acupuncture mechanisms in hypertension, some limitations persist. Individual variability in responses, the need for standardized protocols, and integration with conventional therapies require additional investigation. Furthermore, larger-scale randomized clinical trials are needed to confirm efficacy and establish precise therapeutic guidelines.