Long-loop pathways in cardiovascular electroacupuncture responses

Abstract

Li P, Tjen-A-Looi SC, Guo Z, Fu L, Longhurst JC. Long-loop pathways in cardiovascular electroacupuncture responses. J Appl Physiol 106: 620 -630, 2009. First published December 12, 2008 doi:10.1152/japplphysiol.91277.2008.-We have shown that electroacupuncture (EA) at P 5-6 (overlying median nerves) activates arcuate (ARC) neurons, which excite the ventrolateral periaqueductal gray (vlPAG) and inhibit cardiovascular sympathoexcitatory neurons in the rostral ventrolateral medulla (rVLM). To investigate whether the ARC inhibits rVLM activity directly or indirectly, we stimulated the splanchnic nerve to activate rVLM neurons. Micropipettes were inserted in the rVLM, vlPAG, and ARC for neural recording or injection. Microinjection of kainic acid (KA; 1 mM, 50 nl) in the ARC blocked EA inhibition of the splanchnic nerve stimulation-induced reflex increases in rVLM neuronal activity. Microinjection of D,Lhomocysteic acid (4 nM, 50 nl) in the ARC, like EA, inhibited reflex increases in the rVLM neuronal discharge. The vlPAG neurons receive convergent input from the ARC, splanchnic nerve, P 5-6, and other acupoints. Microinjection of KA bilaterally into the rostral vlPAG partially reversed rVLM neuronal responses and cardiovascular inhibition during D,L-homocysteic acid stimulation of the ARC. On the other hand, injection of KA into the caudal vlPAG completely reversed these responses. We also observed that ARC neurons could be antidromically activated by stimulating the rVLM, and that ARC perikarya was labeled with retrograde tracer that had been microinjected into the rVLM. These neurons frequently contained ␤-endorphin and c-Fos, activated by EA stimulation. Therefore, the vlPAG, particularly, the caudal vlPAG, is required for ARC inhibition of rVLM neuronal activation and subsequent EA-related cardiovascular activation. Direct projections from the ARC to the rVLM, which serve as an important source of ␤-endorphin, appear also to exist. arcuate nucleus; ventrolateral periaqueductal gray; rostral ventrolateral medulla; D,L-homocysteic acid; kainic acid CARDIOVASCULAR DISEASE IS the greatest cause of death in middle-aged and elderly North Americans and Europeans. Although western science has developed a number of effective treatment strategies for this disease, treatment is not perfect and often is associated with side effects. As such, there has been increasing interest from the western countries in exploring alternative medicinal treatments and considering new therapies, such as acupuncture, for cardiovascular disease. According to the World Health Organization, acupuncture is effective in more than 40 medical conditions, including cardiac pain and hypertension (24). Experimental studies have shown that lowcurrent, low-frequency electroacupuncture (EA) employed over deep nerves, like P 5-6 (pericardial meridian) overlying the median nerve, effectively inhibits cardiovascular sympathoexcitatory reflexes and the rostral ventrolateral medulla (rVLM) presympathetic neuronal responses. Conversely, electrical stimulation ...

Electroacupuncture modulates vlPAG release of GABA through presynaptic cannabinoid CB1 receptors

“…Previous neuronal electrophysiological and pharmacological studies from our group (29,30,50) suggest that EA increases vlPAG glutamate, since EA at P5-6 increases splanchnic nerve stimulation of vlPAG neuronal activity and because microinjection of DLH into the vlPAG decreases blood pressure and the rVLM neuronal activity. However, in the present study we did not observe an increase in glutamate in the vlPAG during EA.…”

“…Electroacupuncture modulates vlPAG release of GABA through presynaptic cannabinoid CB1 receptors. J Appl Physiol 106: 1800 -1809, 2009. First published April 9, 2009 doi:10.1152/japplphysiol.91648.2008.-Previous studies have demonstrated that electroacupuncture (EA) attenuates sympathoexcitatory reflex responses by activating a long-loop pathway involving the hypothalamic arcuate nucleus (ARC), midbrain ventrolateral periaqueductal gray (vlPAG), and rostral ventrolateral medulla (rVLM).…”

The hypothalamic arcuate nucleus: a new site of cardiovascular action of angiotensin-(1–12) and angiotensin II

“…The mechanism of this excitation is not clear at this time and may involve pre-and/or postsynaptic effects of ANG-(1-12). Direct projections from the ARCN to the PVN, raphe nuclei, rostral ventrolateral medullary pressor area, and intermediolateral cell column of the thoracolumbar cord may mediate the increases in MAP, HR, and GSNA elicited by microinjections of ANG- (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) into the ARCN (6,9,25,43). We (31) have previously shown that pressor responses elicited by microinjections of NMDA into the ARCN are mediated via the activation of ionotropic glutamate receptors (iGLURs) in the spinal cord.…”

GABA in nucleus tractus solitarius participates in electroacupuncture modulation of cardiopulmonary bradycardia reflex

“…Surgical and experimental protocols were approved by the Animal Use and Care Committee at the University of California, Irvine. Adult male Sprague-Dawley rats (350 -500 g) were used for microinjection of a retrogradely transported microsphere tracer in the nucleus ambiguus to evaluate direct projections from the NTS to the nucleus ambiguus, as described in detail in our previous studies (23). Ketamine-xylazine (80/12 mg/ml, Sigma, St. Louis, MO) was used to induce (0.3-0.4 ml im) and maintain (0.1-0.2 ml im) anesthesia in the animals.…”

“…Modulation of cardiovascular function and elevated sympathetic activity is effective with low frequency and voltage stimulation of electroacupuncture (EA) at specific acupoints P5-6 positioned to activate the underlying median nerves (44 -46). Bilateral stimulation of P5-6 acupoints activates thinly myelinated and unmyelinated sensory fibers in the median nerve and neural pathways that project to cardiovascular-related regions in the central nervous system, which regulate autonomic activity and hence hemodynamic responses (21,23,39). Nuclei in the hypothalamus, midbrain, and medulla process this somatic input during EA to modulate sympathoexcitatory reflex responses (26,28,43).…”