Role of medullary GABA, opioids, and nociceptin in prolonged inhibition of cardiovascular sympathoexcitatory reflexes during electroacupuncture in cats.
Electroacupuncture (EA) causes prolonged suppression of reflex elevations in blood pressure for 1-2 h in anesthetized preparations. A long-loop pathway involving the arcuate nucleus (ARC), ventrolateral periaqueductal gray, and rostral ventrolateral medulla (rVLM) is involved in sympathoinhibitory cardiovascular EA effects. However, the mechanisms and locations of the prolonged EA inhibition are unknown. We hypothesized that this effect is mediated through a long-loop pathway involving opioid, nociceptin, and gamma-aminobutyric acid (GABA) receptor activation in the rVLM. In anesthetized, ventilated cats application of bradykinin to the gallbladder every 10 min induced consistent reflex increases in blood pressure. Bilateral EA stimulation at the cardiovascular acupoints P5-6 overlying the median nerves reduced the reflex responses for at least 80 min. Bilateral blockade with kynurenic acid in the ARC 60 min after onset of EA inhibition reversed the cardiovascular response, suggesting a role for the ARC in the long-loop pathway during the prolonged inhibitory response. Unilateral microinjection with either an opioid or a GABA(A) antagonist in rVLM 50-60 min after the beginning of the EA response reversed EA inhibition of the cardiovascular excitatory reflex. Gabazine also reversed EA inhibition of cardiovascular premotor sympathetic rVLM neurons. Conversely, microinjection of a nociceptin/orphanin FQ peptide antagonist did not affect the prolonged inhibitory effect. Thus the ARC, an important component in the long-loop pathway in the EA cardiovascular response, is required for 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.
Tjen-A-Looi
Stephanie C
SC
Department of Medicine, Susan Samueli Center for Integrative Medicine, School of Medicine, University of California-Irvine, CA 92697-4075, USA. stjenalo@uci.edu
Li
Peng
P
Longhurst
John C
JC
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure; D001920:Bradykinin / Q000378:metabolism; D002319:Cardiovascular System / Q000294:innervation*; D002415:Cats; D015671:Electroacupuncture; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D005704:Gallbladder / Q000294:innervation; D007736:Kynurenic Acid / Q000494:pharmacology; D008475:Median Nerve / Q000502:physiology; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects; D009434:Neural Pathways / Q000378:metabolism; D018847:Opioid Peptides / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D001920:Bradykinin; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D007736:Kynurenic Acid; D009270:Naloxone; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010455:Peptides; D011724:Pyridazines; D011963:Receptors, GABA-A; D011957:Receptors, Opioid; D005680:gamma-Aminobutyric Acid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C049853:gabazine