- The meridian system is the central theory of acupuncture, and serves as a guiding principle for diagnosis and treatment of many alternative therapies. Investigators have demonstrated in both humans and animals that acupoints/meridians possess characteristics of low electric resistance. The principal investigator has recently found that neuronal nitric oxide synthase (nNOS) protein levels and nitric oxide (NO) content are consistently increased in the three meridian skin regions containing low skin resistance points (LSRP) in rats. The principal investigator's histochemical examinations reveal that nNOS expression is markedly increased in nerve fibers, axons, neurons, and hair follicles in the meridians/acupoints. Consistent with the postulated role of NO, LSRP are manifested in rats and normal mice. In contrast, in nNOS knockout mice the resistance is increased. Furthermore, preliminary data show that exogenous NO reduces the resistance in LSRP while the responses are attenuated by blockade of noradrenergic function. The principal investigator hypothesizes that 1) NO is an important meridian chemical and enhanced nNOS expression in the skin is a histochemical marker of meridian/acupoint structures, and 2) NO increases NE release which locally facilitates sympathetic function and mediates the biophysical characteristics of acupoints/meridians. In view of the critical importance and unexplored territory of the meridian system, the major goals of this proposal are: 1) Are nNOS-NO levels selectively increased in the acupoints and/or in the meridian regions? 2) Does L-arginine-derived NO synthesis and acupuncture modify NO release in acupoints/meridians? 3) What are the distributions of nNOS expression in the LSRP and meridian lines? 4) Are nNOS expressions and the skin resistance abolished/reduced in the LSRP of nNOS knockout mice? And 5) does L-arginine-derived NO synthesis increase turnover of NE that mediates biophysical characteristics of acupoints/meridians? The proposed studies will examine localization of nNOS expression, combined with structural analysis of the skin tissues with or without LSRP/meridians detected by electrical methods. Quantification of nNOS protein, mRNA, NE, and NO metabolites will be integrated with neuropharmacological manipulations and electrophysiological examination of LSRP to test the hypotheses in rats, genetically-altered mice, and humans. The results should advance the understanding of the roles of nNOS-NO on a neurochemical, morphological, and functional basis for meridians/acupoints, and yield new insights regarding the effects of NO on noradrenergic activation that mediates the biophysical characteristics of acupoints/meridians.

National Institute of Health (NIH)
National Center for Complementary & Alternative Medicine (NCCAM)
Research Project (R01)
Project #
Application #
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
Wong, Shan S
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
La Biomed Research Institute/ Harbor UCLA Medical Center
United States
Zip Code
Ma, Sheng-Xing; Li, Xi-Yan; Sakurai, Tokusho et al. (2007) Evidence of enhanced non-enzymatic generation of nitric oxide on the skin surface of acupuncture points: An innovative approach in humans. Nitric Oxide 17:60-8
Chen, Jia-Xu; Ibe, Basil O; Ma, Sheng-Xing (2006) Nitric oxide modulation of norepinephrine production in acupuncture points. Life Sci 79:2157-64
Ma, Sheng-Xing; Ma, Jun; Moise, Georgette et al. (2005) Responses of neuronal nitric oxide synthase expression in the brainstem to electroacupuncture Zusanli (ST 36) in rats. Brain Res 1037:70-7
Chen, Jia-Xu; Ma, Sheng-Xing (2005) Effects of nitric oxide and noradrenergic function on skin electric resistance of acupoints and meridians. J Altern Complement Med 11:423-31
Ma, Sheng-Xing; Ji, Ang; Pandjaitan, Marintan et al. (2003) Enhanced nitric oxide release/synthesis in the posterior hypothalamus during nitroglycerin tolerance in rats. Eur J Pharmacol 472:179-87
Ma, Sheng-Xing; Fang, Qun; Morgan, Brian et al. (2003) Cardiovascular regulation and expressions of NO synthase-tyrosine hydroxylase in nucleus tractus solitarius of ovine fetus. Am J Physiol Heart Circ Physiol 284:H1057-63
Chen, Shuang; Ma, Sheng-Xing (2003) Nitric oxide in the gracile nucleus mediates depressor response to acupuncture (ST36). J Neurophysiol 90:780-5
Ma, Sheng-Xing; Li, Xi-Yan (2002) Increased neuronal nitric oxide synthase expression in the gracile nucleus of brainstem following electroacupuncture given between cutaneous hindlimb acupuncture points BL 64 & BL 65 in rats. Acupunct Electrother Res 27:157-69