Previous clinical and experimental studies suggest that acupuncture helps myocardial ischemia, hypertension and arrhythmias. To investigate mechanisms that underlie the cardiovascular influence of acupuncture, we have developed a feline model of reversible myocardial ischemia. Ischemia was induced by partial ligation of a coronary artery and stimulation of a sympathetic reflex induced by bradykinin applied to the gallbladder (GB). We superimposed low frequency (2 - 5 Hz), low intensity (2-5 mA) electroacupuncture (EA) to stimulate bilaterally the Neiguan acupoints, located on the pericardial meridian over the median nerves (MN) on each forelimb. EA for 30 min substantially reduced myocardial ischemia, measured as an improvement in regional myocardial wall thickening, a response requiring 10-20 min for onset and lasting for 60-90 min. Direct MN stimulation as well as stimulation from an acupuncture needle placed percutaneously at the Neiguan acupoints cause similar responses by stimulating Group III more than Group IV fibers in the MN. We also showed that EA works through the endogenous opioid system, since both intravenous and microinjected naloxone into the rostral ventral lateral medulla (rVLM) prevent the EA-related response. Finally, opioid mu and delta, but not K, receptors in the rVLM are responsible for the EA-related modulation of sympathetic outflow, suggesting that endorphins and enkephalins, but not dynorphins are the neuromodulators involved in this response. Current studies are focused on the cellular responses in rVLM neurons. Thus, EA stimulates mainly Group III fibers that ascend to the central nervous system and, through an opioid mechanism in the rVLM, particularly involving endorphins and enkephalins, EA inhibits sympathetic outflow to reduce the pressor response and resulting myocardial ischemia during reflex stimulation. Our studies provide an understanding of the physiological mechanisms underlying EA and assist in developing a framework of information that can be understood and, hopefully, accepted by scientists and clinicians in the Western countries. (C) 2002 Elsevier Science B.V. All rights reserved.