Naloxone reverses inhibitory effect of electroacupuncture on sympathetic cardiovascular reflex responses

Abstract

Acupuncture and electroacupuncture (EA) have been used in traditional Chinese medicine to treat a wide range of diseases and conditions, including angina pectoris and myocardial infarction. In a feline model of reflex-induced reversible myocardial ischemia, electrical stimulation of the median nerves to mimic EA (Neiguan acupoint) significantly improved ischemic dysfunction, secondary to an inhibitory effect of EA on reflex pressor effects evoked by bradykinin (BK). The central mechanism of EA’s inhibitory effect in this model is unknown. Accordingly, in α-chloralose-anesthetized cats, BK (10 μg/ml) was applied to the gallbladder to elicit a cardiovascular reflex response that significantly ( P < 0.05) increased arterial blood pressure and heart rate; normalized systolic wall thickening (%WTh) of the left ventricle, measured by ultrasonic single-crystal sonomicrometer, increased by 31 ± 11% ( P < 0.05). After ligation of a side branch of the left anterior descending coronary artery, the reflex pressor response to BK resulted in a significant decrease of %WTh (−32 ± 6%) in the ischemic region. When bilateral EA of the Neiguan acupoints was performed, the pressor response to BK was inhibited and regional myocardial function was significantly improved (+19 ± 20%). The inhibitory effects of EA on blood pressure and %WTh were reversed by intravenous injection of naloxone (0.4 mg/kg; n = 9) or microinjection of naloxone (10 nM in 0.1 μl/site; n= 14) into the rostral ventrolateral medulla (rVLM). Thus %WTh with intravenous naloxone was reduced to −13 ± 29% ( P<0.05) during stimulation of the gallbladder. Our results indicate that the inhibitory effect of EA on the BK-induced pressor response and the consequent improvement of ischemic dysfunction is dependent on the activation of opioid receptors, specifically receptors located in the rVLM.

Long-loop pathways in cardiovascular electroacupuncture responses

“…For example, our laboratory has shown that this EA-related inhibition is blocked by nonspecific opioid blockade with naloxone as well as with -and ␦-opioid-receptor antagonism (7,14,29). We thus concluded that naloxone, as well as -and ␦-opioid blockade, in this brain stem region modulates the EA-related cardioinhibitory response.…”

Electroacupuncture modulates vlPAG release of GABA through presynaptic cannabinoid CB1 receptors

“…We have found previously that muscle twitches, evoked by stimulation of large-diameter ␣-motor neurons in the mixed median nerve, are a reliable way to confirm the appropriate amount of current that is necessary to also activate smaller diameter group III and IV sensory fibers in the median nerve. This degree of sensory nerve activation evokes a strong modulatory influence of EA on cardiovascular reflex responses (13,26,27). After the animal had been stabilized for 100 min after probe insertion, EA (1-2 mA, 0.5-ms duration, 2 Hz) was initiated and maintained for 28 min.…”

“…Clinically, EA at the NeiguanJianshi (P5-6) acupoints has been used to treat cardiovascular diseases in Eastern and, more recently, Western countries (5, 21, 41). We and others have demonstrated that EA at P5-6 acupoints overlying the median nerve on the wrist modulate blood pressure elevation evoked by gastric distension (GD) in rats (27) or by gallbladder stimulation in cats (50) through a long-loop neural pathway, extending from the arcuate nucleus (ARC) in the hypothalamus to the ventrolateral periaqueductal gray (vlPAG) in the midbrain and, ultimately, to the rostral ventrolateral medulla (rVLM) (13,26,50,58).The midbrain periaqueductal gray (PAG) processes signals concerned with pain and analgesia, fear and anxiety, vocalization, lordosis, and cardiovascular control (9). Previous studies have demonstrated that stimulation of the vlPAG produces depressor responses in cats and rats (32, 33), whereas excitation of the dorsolateral PAG increases blood pressure in cats (16), and as noted above, it is the vlPAG that interacts with the ARC and rVLM in EA modulation of cardiovascular responses (19,30,50).…”

“…Clinically, EA at the NeiguanJianshi (P5-6) acupoints has been used to treat cardiovascular diseases in Eastern and, more recently, Western countries (5, 21, 41). We and others have demonstrated that EA at P5-6 acupoints overlying the median nerve on the wrist modulate blood pressure elevation evoked by gastric distension (GD) in rats (27) or by gallbladder stimulation in cats (50) through a long-loop neural pathway, extending from the arcuate nucleus (ARC) in the hypothalamus to the ventrolateral periaqueductal gray (vlPAG) in the midbrain and, ultimately, to the rostral ventrolateral medulla (rVLM) (13,26,50,58).…”

Stop Hypertension With the Acupuncture Research Program (SHARP)

“…19,20 Mechanistic studies have demonstrated effects of acupuncture on the activity and plasma concentrations of blood pressure modulators, including: renin, aldosterone, angiotensin II, norepinephrine, serotonin, enkephalins, and ␤-endorphins. [21][22][23][24][25][26][27][28][29] The efficacy of acupuncture for treating hypertension is suggested by a large number of published case series and uncontrolled trials. 22,23,25,30 -32 Three randomized trials [33][34][35] reported significant reductions in BP relative to randomly assigned control groups treated for 4 to 8 weeks, whereas 3 others did not report significant effects of acupuncture relative to control subjects.…”