Adenosine A2A receptors in the rostral ventrolateral medulla participate in blood pressure decrease with electroacupuncture in hypertensive rats.

Acupuncture is increasingly used to manage high blood pressure (BP) as a complementary therapy. However, the mechanisms underlying its hypotensive effects remain unclear. Our previous studies have shown that electroacupuncture (EA) at the ST36-37 acupoints, overlying the deep peroneal nerve, attenuates pressor responses through adenosine A2A receptors (A2AR) in the rostral ventrolateral medulla (rVLM). However, it is uncertain whether rVLM A2AR contributes to EA's BP-lowering effect in sustained hypertension. We hypothesized that a course of EA treatment lowers BP, in part, through the activation of adenosine A2AR in the rVLM in hypertensive rats. To mimic essential hypertension in the clinic, we performed EA in conscious Dahl salt-sensitive hypertensive rats (DSHRs). EA (0.1-0.4 mA, 2 Hz) was applied at ST36-37 for 30 min twice weekly for four weeks, while sham-EA was conducted in a similar manner but without electrical input. In hypertensive rats, BP was reduced by EA (n = 14) but neither by sham-EA (n = 14) nor in the absence of needling (n = 8). Following four weeks of eight treatments and then under anesthesia, EA's modulatory effect on elevated BP was reversed by unilateral rVLM microinjection of SCH 58261 (1 mM in 50 nl; an A2AR antagonist; n = 7; P < 0.05) but not the vehicle (n = 5) in EA-treated DSHRs. Activation of rVLM A2AR in DSHRs treated with sham-EA by an A2AR agonist, CGS-21680 (0.4 mM in 50 nl; n = 8), decreased BP. Unilateral administration of SCH 58261 or CGS-21680 into the rVLM did not alter basal BP in Dahl salt-sensitive rats fed a regular diet with normal BP. The A2AR level in the rVLM after EA was increased compared to the sham-EA and untreated DSHRs (n = 5 in each group; all P < 0.05). These data suggest that a 4-week twice weekly EA treatment reduced BP in salt-sensitive hypertensive rats likely through adenosine-mediated A2AR in the rVLM.

Role of TRPV1 in acupuncture modulation of reflex excitatory cardiovascular responses.

We have shown that acupuncture, including manual and electroacupuncture (MA and EA), at the P5-6 acupoints stimulates afferent fibers in the median nerve (MN) to modulate sympathoexcitatory cardiovascular reflexes through central regulation of autonomic function. However, the mechanisms underlying acupuncture activation of these sensory afferent nerves and their cell bodies in the dorsal root ganglia (DRG) are unclear. Transient receptor potential vanilloid type 1 (TRPV1) is present in sensory nerve fibers distributed in the general region of acupoints like ST36 and BL 40 located in the hindlimb. However, the contribution of TRPV1 to activation of sensory nerves by acupuncture, leading to modulation of pressor responses, has not been studied. We hypothesized that TRPV1 participates in acupuncture's activation of sensory afferents and their associated cell bodies in the DRG to modulate pressor reflexes. Local injection of iodoresiniferatoxin (Iodo-RTX; a selective TRPV1 antagonist), but not 5% DMSO (vehicle), into the P6 acupoint on the forelimb reversed the MA's inhibition of pressor reflexes induced by gastric distension (GD). Conversely, inhibition of GD-induced sympathoexcitatory responses by EA at P5-6 was unchanged after administration of Iodo-RTX into P5-6. Single-unit activity of Group III or IV bimodal afferents sensitive to both mechanical and capsaicin stimuli responded to MA stimulation at P6. MA-evoked activity was attenuated significantly ( P < 0.05) by local administration of Iodo-RTX ( n = 12) but not by 5% DMSO ( n = 12) into the region of the P6 acupoint in rats. Administration of Iodo-RTX into P5-6 did not reduce bimodal afferent activity evoked by EA stimulation ( n = 8). Finally, MA at P6 and EA at P5-6 induced phosphorylation of extracellular signal-regulated kinases (ERK; an intracellular signaling messenger involved in cellular excitation) in DRG neurons located at C7-8 spinal levels receiving MN inputs. After TRPV1 was knocked down in the DRG at these spinal levels with intrathecal injection of TRPV1-siRNA, expression of phosphorylated ERK in the DRG neuron was reduced in MA-treated, but not EA-treated animals. These data suggest that TRPV1 in Group III and IV bimodal sensory afferent nerves contributes to acupuncture inhibition of reflex increases in blood pressure and specifically plays an important role during MA but not EA.