Electroacupuncture modulation of reflex hypertension in rats: role of cholecystokinin octapeptide

Am J Physiol Regul Integr Comp Physiol. 2013 Aug 15;305(4):R404-13. doi: 10.1152/ajpregu.00196.2013. Epub 2013 Jun 19.

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.

Keywords: acupuncture; nonresponders; rostral ventrolateral medulla; sympathoexcitation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure* / drug effects
  • Devazepide / administration & dosage
  • Disease Models, Animal
  • Electroacupuncture*
  • Enkephalins / metabolism
  • Hormone Antagonists / administration & dosage
  • Hypertension / etiology
  • Hypertension / metabolism
  • Hypertension / physiopathology
  • Hypertension / prevention & control*
  • Male
  • Mechanotransduction, Cellular*
  • Medulla Oblongata / drug effects
  • Medulla Oblongata / metabolism*
  • Medulla Oblongata / physiopathology
  • Microinjections
  • Narcotic Antagonists / administration & dosage
  • Pressure
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cholecystokinin A / antagonists & inhibitors
  • Receptor, Cholecystokinin A / metabolism
  • Reflex*
  • Sincalide / administration & dosage
  • Sincalide / metabolism*
  • Stomach / innervation*
  • Time Factors

Substances

  • Enkephalins
  • Hormone Antagonists
  • Narcotic Antagonists
  • Receptor, Cholecystokinin A
  • Devazepide
  • Sincalide