Low-frequency electroacupuncture (EA) stimulation of hindlimb acupoints produces long-lasting sympathoinhibition in humans and rats. The gracile nucleus receives primary afferents projecting from the hindlimb, and stimulation of somatic sensory nerves results in changes in sympathetic nerve activity and arterial blood pressure. We have found that neuronal nitric oxide synthase (nNOS) expression in the gracile nucleus is markedly increased in old Fischer rats and reduced in spontaneously hypertensive rats. Our recent studies show that nNOS expression in the gracile nucleus is enhanced by low frequency EA applied to the hindlimb acupoints in rats accompanied by increase nNOS protein level. Preliminary results demonstrate that microinjection of either a nitric oxide (NO) donor or L-arginine into the gracile nucleus alters cardiovascular responses to EA stimulation of the acupoints. Spinothalamic tract cells located in the gracile nucleus are activated by a single electrical stimulus to the sciatic nerve while synaptic transmission through the dorsal column is depressed by a gamma-aminobutyric acid (GABA)-mediated depolarization of the gracile afferents. The purpose of the proposed research is to study our hypotheses that EA stimulation of hindlimb acupoints induces up-regulation of nNOS expression in the gracile nucleus, and the nNOS-NO-GABA system acts as an inhibitory modulation of cardiovascular functions in the gracile-thalamic pathways. The major aims are to determine: 1) Does NO in the gracile nucleus modify the sympatho- and cardiovascular responses to EA applied to the hindlimb acupoints? 2) Does GABAergic transmission mediate the inhibitory responses of NO on EA stimulation in the gracile nucleus? 3) Do time- and concentration-responses to EA-induced endogenous NO release in the gracile nucleus parallel the sympatho- and cardiovascular responses? 4) Is nNOS expression in the gracile nucleus selectively up-regulated by the EA? And 5) What are the distributions of Fos/nNOS expression in the gracile-thalamic pathways induced by the EA? The physiological recordings of arterial blood pressure, heart rate, and renal sympathetic nerve activity will incorporate with EA stimulation and neuropharmacological manipulations and histochemical studies to test the hypotheses in rat models. The results should advance our understanding of the sites and influences of low-frequency EA applied to the hindlimb acupoints on nNOS regulation in the gracile nucleus, and yield new insights regarding central mechanisms of NO and EA on sympathoinhibition.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Exploratory/Developmental Grants (R21)
Project #
3R21AT000209-01S1
Application #
6449754
Study Section
Special Emphasis Panel (ZAT1 (02))
Program Officer
Wong, Shan S
Project Start
2000-04-03
Project End
2003-03-31
Budget Start
2000-04-03
Budget End
2003-03-31
Support Year
1
Fiscal Year
2001
Total Cost
$1,652
Indirect Cost
City
Torrance
State
CA
Country
United States
Zip Code
90502