Effects of Nitric Oxide Synthase Inhibition on Cutaneous Vasodilation in Response to Acupuncture Stimulation in Humans

Kimura, Ken‐ichi; Takeuchi, Hayato; Yuri, Kuniko; Wakayama, Ikuro

doi:10.1136/acupmed-2012-010177

Cited by 23 publications

(17 citation statements)

References 37 publications

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“…L-arginine-derived NO synthesis increases low resistance characteristics of acupoints [37], and norepinephrine turnover rate in acupoints/meridians is facilitated by presence of NO [38]. Consistently, cutaneous vasodilation induced by acupuncture stimulation in the forearms of humans is attenuated by application of NO synthesis inhibitor, which suggest that L-arginine-derived NO synthesis contributes to cutaneous vasodilation induced by acupuncture stimulation [39]. The present results support the possibility that TENS-induced NO generation/release is through L-arginine-derived NO synthesis, since the cumulative NO that mainly comes from non-enzymatic NO generation was already removed by the 1 st biocapture.…”

Section: Discussionmentioning

confidence: 99%

Transcutaneous Electrical Stimulation Increased Nitric Oxide-Cyclic GMP Release Biocaptured Over Skin Surface of Pericardium Meridian and Acupuncture Points in Humans

Ma¹,

Mayer²,

Lee³

et al. 2015

acupunct electrother res

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Objectives The purpose of this study was to consecutively capture and quantify nitric oxide (NO) and cGMP, the second messenger of NO, over the skin surface of acupuncture points (acupoints), meridian line without acupoint, and non-meridian control regions of the Pericardium meridian (PC) in humans, and investigate their response to transcutaneous electrical nerve stimulation (TENS). Design, setting, and main outcome measures Adhesive biocapture tubes were attached to the skin surface along PC regions and injected with 2-Phenyl-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl solution, an NO-scavenging compound, contacting the skin surface for 20 minutes each during 4 consecutive biocapture intervals. TENS (1.0 mA, 6 Hz, 1.0 msec duration) was applied over acupoints PC 8 and PC 3 during the 2nd biocapture for 20 min. Total nitrite and nitrate (NOx-), the stable metabolic products of NO, and cGMP in biocaptured samples were quantified using chemiluminescence and ELISA. Results NOx- levels in the 1st biocapture over PC regions are almost two fold higher compared to subsequent biocaptures and are higher over PC acupoints versus non-meridian control region. Following TENS, NOx- concentrations over PC regions were significantly increased, and cGMP is predominantly released from the skin surface of PC acupoints. Conclusions TENS induces elevations of NO-cGMP concentrations over local skin region with a high level at acupoints. The enhanced signal molecules improve local circulation, which contributes to beneficial effects of the therapy.

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Section: Discussionmentioning

confidence: 99%

Transcutaneous Electrical Stimulation Increased Nitric Oxide-Cyclic GMP Release Biocaptured Over Skin Surface of Pericardium Meridian and Acupuncture Points in Humans

Ma¹,

Mayer²,

Lee³

et al. 2015

acupunct electrother res

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show abstract

“…Our previous studies demonstrated that NO synthase protein levels and NO contents are increased in skin tissue containing acupoints/meridian lines in rats [19–21]. Recent studies demonstrated that low-frequency electroacupuncture induces significant NO release following dermal microdialysis in the acupoint [22], and NO contributes to cutaneous vasodilation induced by acupuncture stimulation [23]. Repeated thermal therapy increases immunoreactivity and expression of endothelial NO synthase in the aortas of hamsters [24, 25], and NO level is increased in blood after warm needling in humans [26].…”

Section: Introductionmentioning

confidence: 99%

Response of Local Nitric Oxide Release to Manual Acupuncture and Electrical Heat in Humans: Effects of Reinforcement Methods

Lee

Anderson

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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This study was to examine the influences of manual acupuncture (MA) and electrical heat corresponding to reinforcing methods on nitric oxide (NO) release over the skin regions in humans. A device with collecting solution was taped to the skin surface along pericardium (PC) or lung (LU) meridian. Acupuncture needles were gently inserted into PC 4 with reinforcing stimulation (low force/rate) for 20 minutes in the MA group. LU11 on the finger was heated (43-44°C) by electrical heat for 20 minutes. Biocapture was consecutively conducted for two 20-minute intervals during and after each treatment. Total nitrite and nitrate (NOx−) in the collecting samples were quantified using chemiluminescence in blinded fashion. Baseline NOx− levels are higher and tended to be higher over PC and LU acupoints during the 1st biocapture. NOx− levels over PC regions were consistently increased by MA during both intervals. NOx− concentrations over LU acupoints were increased and tended to be increased by electrical heat in the 1st and 2nd biocapture. The results suggest that reinforcing MA and electrical heat induce NO released from the local skin regions with higher levels at acupoints, which improve local circulation and contribute to the beneficial effects of the therapies.

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“…Kimura, et al (39) reported that acupuncture induces cutaneous vasodilatation in the forearms of humans, which is attenuated by application of NO synthesis inhibitor. It is postulated that acupuncture stimulation improves local circulation and allows for a flush of algesic or sensitizing substances, leading to pain relief.…”

Section: Stimulus-evoked Nitric Oxide Release Over Skin Regionsmentioning

confidence: 99%

Nitric oxide signaling molecules in acupoints: Toward mechanisms of acupuncture

2017

Chin. J. Integr. Med.

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Recent clinical trial studies have demonstrated that the effects of acupuncture on pain improvement are small and no difference between acupuncture points (acupoints) and non-points. Whether acupuncture needles must be inserted in specific points depends on whether acupoint specificity exists that is still not resolved, and is now urgent. Previous anatomical studies have demonstrated that acupoints exist higher number of nerve fibers/trunks, blood vessels, hair follicles, and sweat glands as well as density of the gap junction. Recent evidence shows that nitric oxide (NO) level is elevated in the acupoints/meridians and is associated with an enhanced expression of NO synthase endowed with transient receptor potential vanilloid type-1. There is growing evidence from international groups showing that acupuncture induces NO-mediated vasodilatation, which increases local blood flow and allows for a flush of algesic or sensitizing substances, leading to pain relief. Previous studies, using a novel biocapture system, have demonstrated that NOx- (total nitrite and nitrate) and cGMP concentrations are consistently increased over skin acupuncture points (acupoints) compared to non-meridian control regions (NMCR) in humans. Dermal microdialysis in humans showed that NO-cGMP releases in the subcutaneous tissue of acupoint are higher than those in NMCR and increased by electroacupuncture (EA). Recent studies have demonstrated that low-frequency electrical stimulation and manual acupuncture with low stimulating force and rate produce an elevation of NO release predominantly over acupoints. In contrast, NO levels over the areas of the skin regions are moderately reduced by high-frequency EA stimulation. The reinforcement methods induce an elevation of vasodilator (NO) release over skin, which contribute to local warmness and beneficial effects of EA including pain relief. Although the specificity of acupoints and monitoring the quantitative response to acupuncture require further investigation, the results from anatomical and biochemical studies consistently show that acupoints exist higher levels of NO signaling molecules, and stimulus-evoked NO release is also with a higher level at acupoints. Results suggest that NO signaling molecules contribute to the specificity of acupoints, and selecting well-trained acupuncturetists for using correct acupoints and appropriate parameters should improve acupuncture clinical trial studies.

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Effects of Nitric Oxide Synthase Inhibition on Cutaneous Vasodilation in Response to Acupuncture Stimulation in Humans

Cited by 23 publications

References 37 publications

Transcutaneous Electrical Stimulation Increased Nitric Oxide-Cyclic GMP Release Biocaptured Over Skin Surface of Pericardium Meridian and Acupuncture Points in Humans

Transcutaneous Electrical Stimulation Increased Nitric Oxide-Cyclic GMP Release Biocaptured Over Skin Surface of Pericardium Meridian and Acupuncture Points in Humans

Response of Local Nitric Oxide Release to Manual Acupuncture and Electrical Heat in Humans: Effects of Reinforcement Methods

Nitric oxide signaling molecules in acupoints: Toward mechanisms of acupuncture

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