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Biomedical subjects

Sheng-Xing Ma

Publications and source records attributed to Sheng-Xing Ma.

11 recordsLinked to original sources

Nitric oxide modulation of norepinephrine production in acupuncture points.

The purpose of this study was to examine the levels of norepinephrine (NE) turnover in skin tissues and to determine the effect of nitric oxide (NO) on NE production in acupuncture points (acupoints) and meridians. The rats were pretreated with alpha-methyl-tyrosine methyl ester and intravenously infused with L-(2,3,5,6-(3)H)-tyrosine. Blood was withdrawn and skin tissues were excised from the low skin resistance points, non-acupoint, and non-meridian areas located on leg, arm, or trunk. The results showed that the skin NE concentration and (3)H-NE release in acupoints were significantly higher than those in non-acupoints and non-meridian controls. (3)H-NE releases in the acupoints were increased by intravenous infusion of 2-N,N-diethylamino-diazenolate-2-oxide, an NO donor, but lowered by N(G)-Propyl-L-arginine, an inhibitor of neuronal NO synthesis. NE turnover rates in the acupoints were lower in the NO donor treated group while the inhibitor of NO synthesis reversed the trend. In contrast, NE turnover rates were not altered by NO donor and inhibitor of NO synthesis in non-acupoint and non-meridian control tissues. This is the first evidence that NE turnover was consistently decreased in acupoints and enhanced NE synthesis/release in acupoints were facilitated by presence of an NO donor and inhibited by an inhibitor of NO synthesis. The data suggest that skin NE synthesis/release in acupoints/meridians is increased in skin acupoints, which is modulated by L-arginine-derived NO synthesis in sympathetic nervous system.

Acupuncture Points↗

Responses of neuronal nitric oxide synthase expression in the brainstem to electroacupuncture Zusanli (ST 36) in rats.

Recent studies have reported that l-arginine-derived nitric oxide (NO) in the gracile nucleus modifies the hypotensive responses to electroacupuncture (EA) stimulation of Zusanli (ST 36). The purpose of this study was to examine the influence of EA stimulation of ST 36 on neuronal NO synthase (nNOS) expression in the brainstem nuclei in rats. EA stimulation of ST 36 and a non-acupoint was performed using 3 Hz of stimulation for 10 s every 2 min for a period of 120 min in rats anesthetized with ketamine. Rats in the sham-treated group received surgery and EA needles were placed into the acupoints without performing the stimulation. After 2-h stimulation and sham treatment, animals were perfused with 4% paraformaldehyde. Sections of rat medulla were examined by immunolabeling with a polyclonal antibody directed against nNOS. The brainstem nuclei were also visualized by NADPH-diaphorase histochemistry, a marker of nNOS activity. nNOS expression and NADPH-diaphorase reactivity were quantified by using a microscope with reticule grid to count the number of positive cells over a nucleus. Unilateral EA stimulation of ST 36 in rats caused increases in nNOS immunostained cells in the rostral region of the ipsilateral gracile nucleus, but was not altered in the contralateral gracile nucleus compared with sham-treated rats (P < 0.05, n = 6-7). NADPH-diaphorase-positive cells were also increased in the ipsilateral gracile nucleus of rats with EA stimulation. nNOS immunostaining and NADPH-diaphorase-positive neurons were significantly increased in both ipsilateral and contralateral sides of the medial nucleus tractus solitarius (mNTS) in rats receiving EA ST 36 compared with sham-treated animals (P < 0.05). nNOS immunostaining and NADPH-diaphorase reactivity was neither altered in the gracile nucleus and mNTS of non-acupoint stimulated rats nor other brainstem nuclei in rats with EA ST 36. These results show that nNOS immunoreactivity and NADPH-diaphorase reactivity are consistently increased in the gracile nucleus and the mNTS by EA ST 36. We conclude that EA ST 36 induces nNOS expression in the gracile nucleus and mNTS, and enhanced nNOS-NO in the nuclei may modify central cardiovascular regulation, which contribute to hypotensive effects of acupuncture.

Acupuncture Points↗

Acupuncture and kidney disease.

Acupuncture as a complex therapeutic system has been used to treat a variety of diseases and pathological conditions. Although the exact mechanism(s) of acupuncture remains unknown, some evidence suggests a mechanism initially involving signal transduction through connective tissue, with secondary involvement of other systems including the nervous system. Acupuncture has become increasingly popular in the Western countries as a therapy for pain and several chronic disorders difficult to manage with conventional treatments. Acupuncture and acupuncture-like somatic nerve stimulation have been used in different kidney diseases and several complications related to them. The effect of acupuncture techniques in some kidney diseases is reviewed on the basis of clinical reports as well as mechanisms that may possibly explain the beneficial effects mediated by acupressure/acupuncture. The potential effect of acupressure techniques in renal inflammation and whether these effects could be mediated through the newly identified cholinergic anti-inflammatory pathway are discussed.

Acupuncture Therapy↗

Effects of nitric oxide and noradrenergic function on skin electric resistance of acupoints and meridians.

OBJECTIVES: The objectives of this study were to determine the effects of L-arginine-derived nitric oxide (NO) synthesis and noradrenergic function on skin electrical resistance of acupoints and meridians. DESIGN: Experiments were performed on male Sprague-Dawley rats anesthetized with sodium pentobarbital. Low skin-resistance points (LSRP; BL 56, PC 6, CV 17), non-LSRP positions (along the meridians), and non- LSRP, non-meridian control positions (adjacent to but not along the meridians) were determined on the skin surface by measurements of the skin stimulus-evoked electrical currents. The effects of L-arginine-derived NO synthesis and noradrenergic function on the currents, representing skin electrical resistance, were examined in the LSRP, non-LSRP, and non-meridian control points. RESULTS: The skin stimulus-evoked electrical currents at BL 56 (36.4 +/- 1.4 microA), PC 6 (35.4 +/- 1.2), and CV 17 (33.1 +/- 1.4) were significantly higher than those in non-LSRP and non-meridian control positions (p < 0.01, n = 7). The currents were consistently increased after repeated stimulation along the skin as a function of time. Intravenous injections of L-arginine (3 mg/kg, 10 mg/kg, and 30 mg/kg) and 3-morpholinyl-sydnoneimine (SIN-1; 1 microg/kg, 3 microg/kg, and 10 microg/kg) produced dose-dependent increases in the currents (p < 0.05, n = 5-6), but currents were not altered by injections of D-arginine (3 mg/kg, 10 mg/kg, and 30 mg/kg). Stimulus-evoked increases in currents were blocked by intravenous injections of either N (G)-propyl-L-arginine (NPLA, 3 mg/kg), N-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg), or guanethidine (3 mg/kg), a noradrenergic blockade. CONCLUSIONS: This is the first evidence showing that L-arginine-derived NO synthesis and noradrenergic transmission modify the skin electric conductance of LSRP. L-Arginine-derived NO synthesis appears to mediate noradrenergic function on skin sympathetic nerve activation, which contributes to low resistance characteristics of acupoints and meridians.

Acupuncture Points↗

Neurobiology of Acupuncture: Toward CAM.

It has long been accepted that acupuncture, puncturing and scraping needles at certain points on the body, can have analgesic and anesthetic effects, as well as therapeutic effects in the treatment of various diseases. This therapy, including acupuncture anesthesia, has drawn the attention of many investigators and become a research subject of international interest around the world. Numerous studies have demonstrated that the nervous system, neurotransmitters, endogenous substances and Jingluo (meridians) may respond to needling stimulation and electrical acupuncture. An abundance of information has now accumulated concerning the neurobiological mechanisms of acupuncture, in relation to both neural pathways and neurotransmitters/hormonal factors that mediate autonomic regulation, pain relief and other therapeutics. Early studies demonstrated that the analgesic effects of electroacupuncture (EA) are mediated by opioid peptides in the periaqueductal gray. Recent evidence shows that nitric oxide plays an important role in mediating the cardiovascular responses to EA stimulation through the gracile nucleus-thalamic pathway. Other substances, including serotonin, catecholamines, inorganic chemicals and amino acids such as glutamate and alpha-aminobutyric acid (GABA), are proposed to mediate certain cardiovascular and analgesic effects of acupuncture, but at present their role is poorly understood. The increased interest in acupuncture health care has led to an ever-growing number of investigators pursuing research in the processes of the sense of needling touch, transduction of needling stimulation signals, stimulation parameters and placebos. In this Review, the evidence and understanding of the neurobiological processes of acupuncture research have been summarized with an emphasis on recent developments of nitric oxide mediating acupuncture signals through the dorsal medulla-thalamic pathways.

Journal Article↗

Enhanced nitric oxide release/synthesis in the posterior hypothalamus during nitroglycerin tolerance in rats.

We have recently observed that increasing central noradrenergic transmission and sympathomimetic activity is involved with the complex hemodynamic effects during tolerance to nitroglycerin. The present study was to examine the release of nitric oxide (NO) in the posterior hypothalamus during tolerance to depressor responses to nitroglycerin and determine if, during the tolerance, endogenous NO synthesis is induced in the posterior hypothalamus. A microdialysis probe was implanted in the posterior hypothalamus and perfusion fluid was pumped through the probe at 2 microl/min in conscious rats. Tolerance to nitroglycerin was produced by three intravenous (i.v.) injections of 1.3 mg nitroglycerin each within 40 min compared to the same administrations of low dose of the drug, sodium nitroprusside and papaverine. Dialysate samples were collected 1 h before and 1 h each after injections for 8 h. Concentrations of nitrite (NO(2)(-)), nitrate (NO(3)(-)), and total nitrite plus nitrate (NO(x)(-)) were quantified in the samples by using chemiluminescence. The dose-response curve for arterial depressor induced by intravenous injection of the challenge doses of nitroglycerin was markedly shifted to the right at the first hour after nitroglycerin tolerance, lasted 3 to 5 h and reversed at 7 h. The dialysate NO(3)(-) and NO(x)(-) concentrations in the posterior hypothalamus were significantly increased at the first hour following nitroglycerin tolerance but were not altered by low dose of the drug, sodium nitroprusside, and papaverine. Nitroglycerin tolerance predominantly caused an increase in NO(3)(-) release in the posterior hypothalamus with no or small amount of changes in dialysate NO(2)(-) and the response was partially inhibited by pretreatment with N(G)-Propyl-L-arginine (NPLA) (1.0 mg/kg, i.p.), an inhibitor of neuronal NO synthesis. The increase of NO release in the posterior hypothalamus occurred at the first hour, lasted 2 to 3 h and reversed at 5 to 6 h during nitroglycerin tolerance. The results show that systemically administered high dose of nitroglycerin increases NO release in the posterior hypothalamus which matches the time interval of tolerance to arterial depressor response to the drug. Data suggest that there is an enhanced endogenous NO synthesis in the posterior hypothalamus which may affect central sympathetic functions during nitroglycerin tolerance.

Animals↗

Nitric oxide in the gracile nucleus mediates depressor response to acupuncture (ST36).

The purpose of these studies was to determine the role of gracile nucleus and the effects of l-arginine-derived nitric oxide (NO) synthesis in the nucleus on the cardiovascular responses to electroacupuncture (EA) stimulation of "Zusanli" (ST36). Arterial blood pressure and heart rate were monitored during EA stimulation of ST36 following microinjections of agents into gracile nucleus. EA ST36 produced depressor and bradycardiac responses in anesthetized Sprague-Dawley rats. The cardiovascular responses to EA ST36 were blocked by bilateral microinjection of lidocaine into gracile nucleus. Microinjection of L-arginine into gracile nucleus facilitated the hypotensive and bradycardiac responses to EA ST36. The cardiovascular responses to EA ST36 were attenuated by bilateral microinjection of neuronal NO synthase (nNOS) antisense oligos into gracile nucleus. Microinjection of nNOS sense oligos into gracile nucleus did not alter the cardiovascular response to EA ST36. The results demonstrate that a blockade of neuronal conduction in the gracile nucleus inhibits the cardiovascular responses to EA ST36. The hypotensive and bradycardiac responses to EA ST36 are modified by influences of L-arginine-derived NO synthesis in the gracile nucleus. We conclude that NO plays an important role in mediating the cardiovascular responses to EA ST36 through gracile nucleus.

Animals↗

Enhanced nitric oxide concentrations and expression of nitric oxide synthase in acupuncture points/meridians.

OBJECTIVES: The objectives of this study were to examine the distributions of nitric oxide (NO) in the skin points (acupoints)/meridian regions and determine whether neuronal nitric oxide synthase (nNOS) protein levels were associated with NO concentrations in the areas. DESIGN: Low skin resistance points (LSRP) on the skin surface in response to electrical stimuli were performed in anesthetized adult rats. The skin together with subcutaneous tissue was isolated in meridian regions from PC 2 to 6, BL 36 to 57, CV 3 to 22, and GV 2 to 14. Control skin tissues were obtained in the areas close to related meridians without containing LSRP. Concentrations of nitrite (NO(2)(-)), nitrate (NO(3)(-)), and total NO(2)(-) plus NO(3)(-) (NO(x)(-)) were quantified in the skin tissues, micropunches of brain nuclei, and blood vessels in a blinded fashion. Western blots were also conducted using polyclonal anti-nNOS and anti-endothelial nitric oxide synthase (eNOS) antibody in the skin tissues. RESULTS: NO(x)(-) and NO(3)(-) concentrations were higher (45 +/- 8% and 43 +/- 7% in the CV, 47 +/- 7% and 51 +/- 9% in the BL, and 47 +/- 8% and 45 +/- 6% in the PC) than those in control regions (p < 0.05, n = 6). NO(x)(-) concentrations are 2- to 3-fold greater in skin tissues than those in brain regions and blood vessels (p < 0.05, n = 6-8). nNOS protein levels were consistently increased in the skin regions of BL, PC, and GV meridians compared with their controls (p < 0.05, n = 5-7) but endothelial NO synthase expression was not changed. CONCLUSION: This is the first evidence showing that NO contents and nNOS expression are consistently higher in the skin acupoints/meridians associated with low electric resistance. The results suggest that enhanced NO in the acupoints/meridians is generated from multiple resources including neuronal NOergic system, and NO might be associated with acupoint/meridian functions including low electric resistance.

Acupuncture Points↗

Cardiovascular regulation and expressions of NO synthase-tyrosine hydroxylase in nucleus tractus solitarius of ovine fetus.

The purpose of this study was to examine cardiovascular responses to fourth cerebral ventricle (4V) administration of nitroglycerin (NTG) or an inhibitor of nitric oxide (NO) synthase (NOS) in the near-term ovine and to determine whether, during birth, neuronal NOS (nNOS) is induced in noradrenergic A1 neurons in the medial nucleus tractus solitarius (mNTS). In chronically instrumented fetal sheep, 4V injection of NTG (1.2 nmol), an NO donor, produced an arterial blood depressor and a moderate decrease in heart rate. Arterial blood pressure is increased by 4V administration of NG-nitro-L-arginine methyl ester (10 nmnol), an inhibitor of NOS, in fetuses. Sections of the medulla from fetuses and newborn lambs were examined by using immunolabeling with tyrosine hydroxylase (TH) antibody combined with NADPH diaphorase (NADPHd) histochemistry, a marker of nNOS activity. The NADPHd-positive cells and TH-positive cells containing NADPHd reactivity were significantly increased in the mNTS of newborns compared with the fetuses. The results suggest that during birth, there is upregulation of NADPHd/nNOS in the noradrenergic neurons of mNTS resulting in a centrally mediated reduction of fetal arterial blood pressure.

Animals↗

Neuronal NO modulates spontaneous and ANG II-stimulated fetal swallowing behavior in the near-term ovine fetus.

Spontaneous fetal swallowing occurs at a markedly higher rate compared with spontaneous adult drinking activity. This high rate of fetal swallowing is critical for amniotic fluid volume regulation. Central NO is critical for maintaining the normal rate of fetal swallowing, as nonselective inhibition of NO (with central N(G)-nitro-L-arginine methyl ester) suppresses spontaneous and angiotensin II (ANG II)-stimulated swallowing. We sought to differentiate the contributions of central endothelial vs. neuronal NO in the regulation of spontaneous and stimulated fetal swallowing, using a selective neuronal NO synthase (nNOS) inhibitor. Six time-dated pregnant ewes and fetuses were chronically prepared with fetal vascular and intracerebroventricular (i.c.v.) catheters and electrocorticogram (ECoG) and esophageal electromyogram electrodes and studied at 130 +/- 1 days of gestation. After an initial 2-h baseline period (0-2 h), the selective nNOS inhibitor N-propyl-L-arginine (NPLA) was injected i.c.v. (2-4 h). At 4 h, the dose of NPLA was repeated, together with ANG II, and fetal swallowing was monitored for a final 2 h. Four fetuses also received an identical control study (on an alternate day) in which NPLA was replaced with artificial cerebrospinal fluid (aCSF). Suppression of nNOS by i.c.v. NPLA significantly reduced mean (+/- SE) spontaneous fetal swallowing (1.35 +/- 0.12 to 0.50 +/- 0.07 swallows/min; P < 0.001). Injection of ANG II in the presence of NPLA had no dipsogenic effect on fetal swallowing (0.68 +/- 0.09 swallows/min). In the aCSF study, i.c.v. aCSF did not change fetal swallowing (0.93 +/- 0.10 vs. 0.95 +/- 0.09 swallows/min), whereas i.c.v. ANG II resulted in a significant increase in the rate of fetal swallowing (2.0 +/- 0.04 swallows/min; P = 0.001). We speculate that the suppressive dipsogenic effects of central NPLA indicate that spontaneous and ANG II- stimulated fetal swallowing is dependent on central nNOS activity.

Angiotensin II↗

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.

This study was to examine the influence of electroacupuncture (EA) stimulation on neuronal nitric oxide synthase (nNOS) expression in the brainstem nuclei in rats. Low-frequency EA stimulation (3 pulses/sec) was applied between 2 acupuncture points (acupoints), Jinggu (BL 64) and Shugu (BL 65) which are cutaneously located at hindlimb, in rats anesthetized with ketamine. After 2 hours stimulation and sham-treatment, animals were perfused with 4% paraformaldehyde. Sections of rat medulla were examined by immunolabeling with a polyclonal antibody directed against nNOS. The brainstem nuclei were also visualized by NADPH-diaphorase histochemistry, a marker of nNOS activity. nNOS levels were quantified by using a microscope with reticule grid to count the number of positive cells over an area. Unilateral EA stimulation of BL 64 and BL 65 in rats caused increases in nNOS immunostaining cells in the ipsilateral and contralateral gracile nucleus compared with sham-treated rats (P<0.05, n=6). NADPH-diaphorase positive cells were also increased in the gracile nucleus of the rats with EA stimulation. Neither nNOS immunostaining nor NADPH-diaphorase reactivity was altered in the nucleus tractus solitarius, rostral ventral medull and other brainstem nuclei in rats with EA stimulation. These results show that nNOS immunoreactivity and NADPH-diaphorase reactivity are consistently increased in the gracile nucleus by low-frequency EA applied to BL 64 and BL 65. We conclude that EA stimulation of the cutaneous hindlimb acupoints induces nNOS expression in the gracile nucleus, and enhanced nNOS-NO in the area may mediate somatosympathetic reflex activities, which contribute to therapeutic effects of acupuncture.

Acupuncture Points↗