- 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.
