Adenosine A2a Receptor Mediated‐inhibitory Effects of Electroacupuncture on Sympathoexcitatory Reflexes Are Associated with Opioids in the Rostral Ventrolateral Medulla of Rats

Abstract

It has been largely demonstrated that electroacupuncture (EA) lowers high blood pressure (BP). However, mechanisms underlying EA's effects on elevated BP remain unclear. Our previous studies have shown that EA attenuates reflex elevation in BP induced by gastric distension (GD) through its influence on rostral ventrolateral medulla (rVLM). Although adenosine is released during neuronal activation in the rVLM, its role in acupuncture‐cardiovascular regulation is unknown. Adenosine A2a rVLM receptors are known to contribute to depressor responses. The action of A2a receptor stimulation in the central nervous system may be regulated through an opioid mechanism. However, it is uncertain whether in the rVLM this putative action occurs. We hypothesized that adenosine in the rVLM contributes to EA modulation of sympathoexcitatory reflexes through an A2a‐opioid receptor mechanism. Repeated GD every 10 min was performed in Sprague‐Dawley male rats under ketamine and α‐chloralose anesthesia. EA (2 Hz, 0.5 ms, 1–4 mA) or sham‐EA (identical procedures as EA without electrical stimulation) was applied at the P5‐6 acupoints, overlying the median nerve, for 30 min after establishing two consistent reflex responses to GDs. We observed that EA (n=5) but not sham‐EA (n=5) at P5‐6 markedly (P<0.05) reduced GD‐induced elevations in BPs. EA modulation of sympathoexcitatory cardiovascular responses was reversed significantly after rVLM microinjection of an A2a receptor antagonist, SCH 58261 (1 mM in 50 nl; n=8; P<0.05), but not by the vehicle (5% dimethylsulfoxide; n=6). Furthermore, microinjection of an A2a receptor agonist, CGS‐21680 (0.4 mM in 50 nl) into the rVLM enhanced EA's inhibitory action (n=8; P<0.05). Blockade of opioid receptors with naloxone (0.1 μM in 50 nl) in the rVLM reversed EA's inhibitory effects on GD‐induced pressor responses and blunted the CGS‐21680‐associated enhancement of EA inhibition (n=6; P<0.05). Neurons labeled with adenosine A2a receptors were co‐localized with neurons stained with enkephalin as well as delta‐opioid receptors in the rVLM. These data suggest that the involvement of rVLM adenosine A2a receptors in EA modulation of GD‐induced pressor reflexes is, at least in part, dependent on the presence of opioids.Support or Funding InformationNCCIH grant, R01 AT009347This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.