Submitted on July 18, 2007
Accepted on September 17, 2007
Role of Medullary GABA, Opioids and Nociceptin in Prolonged Inhibition of Cardiovascular Sympathoexcitatory Reflexes during Electroacupuncture in Cats
Stephanie C Tjen-A-Looi1*, Peng Li2, and John C. Longhurst3
1 Department of Medicine, University of California, College of Medicine, Irvine, California, United States
2 Department of Medicine, University of California, Irvine, Irvine, California, United States
3 Departments of Medicine, Physiology and Biophysics, University of California, Irvine, Irvine, California, United States
* To whom correspondence should be addressed. E-mail: stjenalo{at}uci.edu.
Acupuncture causes prolonged suppression of reflex elevations in blood pressure. For example, 30 min of electroacupuncture (EA) can reduce reflex increases in blood pressure for 1-2 hours in anesthetized preparations. A long-loop pathway involving the arcuate nucleus, ventrolateral periaqueductal gray and rostral ventral lateral medulla (rVLM) is involved in the sympathoinhibitory cardiovascular effects of EA. However, the mechanisms and locations of the prolonged EA inhibition are unknown. We hypothesized that this effect is mediated through a long-loop pathway and involves opioid, nociceptin and γ-amino butyric acid (GABA) receptor activation in the rVLM. Heart rate and mean blood pressure were monitored in anesthetized ventilated cats. Application of bradykinin every 10 min to the gallbladder induced consistent reflex increases in blood pressure. Bilateral stimulation with EA at the cardiovascular acupoints P5-6 (located over the median nerves) reduced the BK-mediated pressor responses for at least 80 min. Bilateral blockade of ionotropic glutamate receptors with kynurenic acid in the arcuate nucleus 60 min after onset of EA-related inhibition reversed the cardiovascular response, suggesting a role for the arcuate nucleus in the long-loop pathway during the prolonged inhibitory response. Additionally, unilateral microinjection with either the non-specific opioid antagonist naloxone or the GABA Aantagonist gabazine in the rVLM 50 to 60 min after the beginning of the EA response both reversed the acupuncture-induced inhibition of the blood pressure reflex. Gabazine also reversed the EA inhibition of cardiovascular premotor sympathetic rVLM neurons. Conversely, microinjection of a nociceptin/orphanin FQ peptide, antagonist ([N-Phe1]-nociceptin(1- 3)NH2) did not affect the prolonged inhibitory effect. Thus, the arcuate nucleus, an important component in the long-loop pathway in the EA-cardiovascular response, is required for the prolonged suppression of reflex cardiovascular excitatory responses by EA. Furthermore, in the rVLM, opioids and GABA, but not nociceptin, participate in the long-term EA-related inhibition of sympathoexcitatory cardiovascular responses.
