We have shown that electroacupuncture (EA) activates arcuate (ARC) neurons, which excite the rostral ventrolateral periaqueductal gray (vlPAG) and inhibit cardiovascular sympathoexcitatory neurons in the rostral ventrolateral medulla (rVLM). To investigate the possibility that the arcuate both directly and indirectly inhibits rVLM activity, we stimulated the splanchnic nerve to activate rVLM neurons. Micropipettes were inserted in the rVLM, vlPAG and arcuate for neural recording or injection. Microinjection of kainic acid (KA, 1 mM, 50 nl) in the arcuate blocked EA inhibition of the reflex increases in rVLM neuronal activity. Microinjection of d,l-homocysteic acid (DLH, 4 nM, 50 nl) in the arcuate, like EA, inhibited reflex increases in the rVLM neuronal discharge. The vlPAG neurons received convergent input from the arcuate, splanchnic nerve, P 5-6 (along pericardial meridian) and other acupoints. Microinjection of KA bilaterally into the rostral vlPAG partially reversed rVLM neuronal responses and cardiovascular inhibition during DLH stimulation of the arcuate. Conversely, injection of KA into the caudal vlPAG completely reversed these responses. However, we also observed that arcuate neurons could be antidromically activated by stimulating the rVLM and that arcuate perikarya 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 EA modulation of rVLM activation and subsequent sympathoexcitatory cardiovascular activation. Direct projections, which provide an important source of -endorphin from the arcuate to the rVLM also appear to exist. These mechanisms require further investigation.