title: Electroacupuncture modulation of reflex hypertension in rats: role of cholecystokinin octapeptide.
abstract: Acupuncture or electroacupuncture (EA) potentially offers a nonpharmacological approach to reduce high blood pressure (BP). However, ~70% of the patients and animal subjects respond to EA, while 30% do not. EA acts, in part, through an opioid mechanism in the rostral ventrolateral medulla (rVLM) to inhibit sympathoexcitatory reflexes induced by gastric distention. CCK-8 opposes the action of opioids during analgesia. Therefore, we hypothesized that CCK-8 in the rVLM antagonizes EA modulation of sympathoexcitatory cardiovascular reflex responses. Male rats anesthetized with ketamine and α-chloralose subjected to repeated gastric distension every 10 min were examined for their responsiveness to EA (2 Hz, 0.5 ms, 1-4 mA) at P5-P6 acupoints overlying median nerve. Repeated gastric distension every 10 min evoked consistent sympathoexcitatory responses. EA at P5-P6 modulated gastric distension-induced responses. Microinjection of CCK-8 in the rVLM reversed the EA effect in seven responders. The CCK1 receptor antagonist devazepide microinjected into the rVLM converted six nonresponders to responders by lowering the reflex response from 21 ± 2.2 to 10 ± 2.9 mmHg (first vs. second application of EA). The EA modulatory action in rats converted to responders with devazepide was reversed with rVLM microinjection of naloxone (n = 6). Microinjection of devazepide in the absence of a second application of EA did not influence the primary pressor reflexes of nonresponders. These data suggest that CCK-8 antagonizes EA modulation of sympathoexcitatory cardiovascular responses through an opioid mechanism and that inhibition of CCK-8 can convert animals that initially are unresponsive to EA to become responsive.
authors.affiliation: Department of Medicine and Susan Samueli Center of Integrative Medicine, University of California, Irvine, California.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Tjen-A-Looi
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Guo
authors.forename: John C
authors.initials: JC
authors.lastname: Longhurst
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D020109:Devazepide / Q000008:administration & dosage; D004195:Disease Models, Animal; D015671:Electroacupuncture; D004745:Enkephalins / Q000378:metabolism; D006727:Hormone Antagonists / Q000008:administration & dosage; D006973:Hypertension / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D040542:Mechanotransduction, Cellular; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008845:Microinjections; D009292:Narcotic Antagonists / Q000008:administration & dosage; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A / Q000037:antagonists & inhibitors / Q000378:metabolism; D012018:Reflex; D012844:Sincalide / Q000008:administration & dosage / Q000378:metabolism*; D013270:Stomach / Q000294:innervation*; D013997:Time Factors
chemical_list: D004745:Enkephalins; D006727:Hormone Antagonists; D009292:Narcotic Antagonists; D043886:Receptor, Cholecystokinin A; D020109:Devazepide; D012844:Sincalide
keywords: acupuncture; nonresponders; rostral ventrolateral medulla; sympathoexcitation