Acupuncture is an effective therapeutic modality in Eastern cultures, but has not achieved widespread recognition as a useful therapeutic option in Western medicine. In addition to its use in pain and anesthesia, electro-acupuncture (EA) has been used in hypertension, hypotension, angina and cardiac arrhythmias. Recently, the Pl's laboratory has begun to explore the physiological basis of EA. An initial study demonstrated that low frequency EA ameliorates myocardial ischemia by reducing myocardial oxygen demand in a feline model of reversible ischemia. In this model, stimulation of gallbladder chemosensitive afferent nerve endings reflexly increased arterial blood pressure, and augmented myocardial oxygen demand, which outstripped coronary blood supply following partial coronary ligation. Concurrent stimulation of the median nerves underlying the Neiguan acupoints reduced myocardial ischemia, measured as a reduction in regional wall thickening. A second study employing EA suggests a role of the endogenous opiate system in the rostral ventral lateral medulla (rVLM). Preliminary data from the Pl's laboratory indicate that the rVLM and periaqueductal gray (PAG) mediate the interaction between visceral (gallbladder) and somatic (EA) afferent nerve stimulation, and suggest a role for mu- and delta-opioid receptors. Also, the Pl has demonstrated in preliminary studies the ability to identify cells in the rVLM that receive convergent input from the greater splanchnic nerve (supplying the gallbladder) and the median nerve. Five hypotheses are now proposed: 1 ) The order of potency for the blood pressure-lowering effect of EA will be mu-equal to or greater than delta-greater than kappa-opioid receptors; 2) Non-NMDA excitatory amino acid receptors are responsible for stimulation of its neuronal subpopulation; 3) EA of Neiguan produces post-synaptic inhibition of an excitatory input to these neurons; 4) The ventrolateral PAG participates in EA modulation of reflex autonomic responses through an opioid mechanism and by influencing sympathoexcitatory rVLM neurons; and 5) Deep but not superficial somatic nerves underlying specific acupoints provide convergent input into rVLM and PAG neurons, and, through an opioid mechanism, modulate neuronal activity. Studies will be conducted in anesthetized cats whose rVLM and PAG are approached stereotaxically for extracellular recording and to deliver pharmacologic antagonists and agonists. Collaboration with both US and Chinese authorities on central neural electrophysiological and acupuncture research will significantly contribute to the ability to accomplish this investigation. By demonstrating the central neural mechanisms underlying this clinically beneficial modification of a cardiovascular reflex response by EA, scientists and clinicians will have a better understanding that will likely aid in acceptance and use of this alternative therapy. The Pl indicates that this project has important clinical implications.