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ABSTRACT: Infrared heat, a transient receptor potential vanilloid type-3 (TRPV3) sensitive stimulus, may have potential physiological effects beneficial to treating metabolic syndrome.
Obesity prone (OP) and obesity resistant (OR) rats were fed for seven days on a high-fat diet. Heat treated OP rats were exposed twice daily to infrared light for 20 min each, separated by 80 min of rest. Food intake, blood pressure, blood glucose, and body weight measurements were taken daily and compared between treated OP rats, untreated OP rats, and OR controls. The animals were perfused with 4% paraformaldehyde, and immunohistochemistry was performed on the coronal brainstem sections with polyclonal antibodies against TRPV3 and pro-opiomelanocortin (POMC). The positive-staining cells in the medulla nuclei were quantified using a microscope with reticule grid.
Food intake, body weight, and mean arterial blood pressure (MAP) were higher in OP rats, a diet-induced metabolic syndrome model, accompanied by a reduced expression of POMC, an anorectic agent, in the hypoglossal nucleus (HN) and medial nucleus tractus solitarius (mNTS). Food intake in heat-treated OP rats was significantly decreased. POMC positive neuron count was increased in the HN and mNTS of OP rats following treatment. TRPV3 positive staining neurons were increased in the HN and mNTS of OP control rats and decreased following the heat treatments.
Lowered POMC and heightened TRPV3 expressions in the HN and mNTS are involved in development of hyperphagia and obesity in OP rats. Exposure to infrared heat modifies TRPV3 and POMC expression in the brainstem, reducing food intake.
International Journal of Hyperthermia 10/2011; 27(7):708-16. · 1.92 Impact Factor
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ABSTRACT: The present study was to examine the distribution of transient receptor potential vanilloid type-1 (TRPV1) receptor immunoreactivity in the acupuncture points (acupoint), and determine the influences of electroacupuncture (EA) stimulation on TRPV1 expression. EA stimulation of BL 40 was conducted in two sessions of 20 min separated by an 80 min interval in anesthetized rats. Sections of skin containing BL 40, and its non-meridian control were examined by immunolabeling with antibodies directed against TRPV1. Without EA, the number of subepidermal nerve fibers expressing TRPV1 was higher in the acupoint than in non-acupoint control skin (p<0.01). The subepidermal nerve fibers showed the co-localization of TRPV1 with peripherine, a marker for the C-fibers and A-δ fibers. The expression of TRPV1 in nerve fibers is significantly increased by EA stimulation in acupoints (p<0.01). However the upregulation in the non acupoint meridian and the non-meridian control skin was short of statistical significance. Double immunostaining of TRPV1 and neuronal nitric oxide synthase (nNOS) revealed their co-localization in both the subepidermal nerve fibers and in the dermal connective tissue cells. These results show that a high expression of TRPV1 endowed with nNOS in subepidermal nerve fibers exists in the acupoints and the expression is increased by EA. We conclude that the higher expression of TRPV1 in the subepidermal nerve fibers and its upregulation after EA stimulation may play a key role in mediating the transduction of EA signals to the CNS, and its expression in the subepidermal connective tissue cells may play a role in conducting the local effect of the EA.
Journal of chemical neuroanatomy 01/2011; 41(3):129-36. · 1.75 Impact Factor
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ABSTRACT: The purposes of these studies were to quantify the concentrations of total nitrate and nitrite (NO(x)(-)) cyclic guanosine monophosphate (cGMP), and nitrotyrosine over skin surface in normal weight healthy volunteers (n = 64) compared to overweight/obese subjects (n = 54). A semi-circular plastic tube was taped to the skin along acupuncture points (acupoints), meridian line without acupoint (MWOP), and nonmeridian control and filled with a 2-Phenyl-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl solution for 20 min. The concentrations of NO(x)(-), cGMP, and nitrotyrosine in the samples were quantified in a blinded fashion using chemiluminescence and enzyme-linked immunosorbent assay, respectively. In normal weight healthy volunteers, NO(x)(-) and cGMP concentrations were consistently increased over the pericardium meridian (PC) 4-7 compared with nonmeridian areas. NO(x)(-) concentration is enhanced over the bladder meridian (BL) 56-57, but cGMP level is similar between the regions. In overweight/obese subjects, NO(x)(-) contents were increased or tended to be elevated over PC and BL regions. cGMP is paradoxically decreased over PC acupoints and nonmeridian control on the forearm but the decreases were blunted along BL regions on the leg. Nitrotyrosine concentrations are markedly elevated (five- to sixfold) over both PC and BL in all areas of overweight/obese subjects. This is the first evidence showing that nitrotyrosine level is tremendously elevated over skin accompanied by paradoxical changes in nitric oxide (NO)-cGMP concentrations over PC skin region in overweight/obese subject. The results suggest that NO-related oxidant inflammation is systemically enhanced while cGMP generation is impaired over PC skin region but not over BL region in obesity.
Obesity 12/2010; 19(8):1560-7. · 4.28 Impact Factor
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ABSTRACT: The purpose of these studies was to examine the effects of electroacupuncture (EA) Zusanli (ST36) on release of nitric oxide (NO) in the gracile nucleus (GN) and determine if functional neuropathic changes were modified by EA ST36-induced NO in the nucleus in Zucker diabetic fatty (ZDF) rats. The foot withdrawal responses to mechanical, thermal and cold stimuli were measured before and after EA stimulation. A microdialysis probe was implanted in the GN and dialysate samples were collected 20 min before, during and after EA ST36. Total nitrate and nitrite (NO(x) (-)) concentrations in the samples were quantified by using chemiluminescence. The baseline dialysate NO(x) (-) concentrations in the GN were decreased in ZDF rats compared to lean control (LC) rats (P < .05). In ZDF rats, dialysate NO(x) (-) releases in the GN were markedly increased during EA ST36, whereas in LC rats, the releases were moderately enhanced at 20-40 min after EA ST36. The withdrawal latencies to mechanical, cold and thermal stimuli were significantly improved 20 min after EA ST36 both in LC and ZDF rats, but not altered by non-acupoint stimulation. The withdrawal latencies to EA ST36 were further potentiated by 3-morpholinyl-sydnoneimine and inhibited by N(G)-Propyl-l-arginine infused into the GN in ZDF rats (P < .05). These results show that EA ST36 increases NO release in the GN, and NO in the nucleus modifies withdrawal latencies to mechanical, cold, and thermal nociception stimuli. Data suggest that EA ST36 induces NO release in the GN, which contributes to improvement of sensory neuropathies in rats.
Evidence-based Complementary and Alternative Medicine 09/2009; 2011:134545. · 4.77 Impact Factor
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ABSTRACT: The aim of this study was to examine the release of nitric oxide (NO) and cGMP in response to electroacupuncture (EA) stimulation in the acupuncture point (acupoint), compared to the non-meridian control area.
Thirty samples of dermal microdialysis data were collected from 24 volunteers at pericardium (PC) 4 and control area. EA was applied to PC 3 by using a 5-V pulse with a duration of 1.0 milliseconds at 10 Hz for 15 minutes. Dialysate samples were continuously collected 20 minutes each before, during, and after EA for two hours. Total nitrite and nitrate (NO(x)(-)) and cGMP in the dialysate were quantified in a blinded fashion.
Dialysate NO(x)(-) concentrations were decreased during a 120-minute dialysis in all groups, but reduced NO(x)(-) levels were attenuated predominantly in PC 4 acupoint at 20-40 minutes after EA PC 3. cGMP concentrations were significantly enhanced in acupoint PC 4 by EA PC 3, but not in the non-meridian area.
We suggest that the attenuation of NO(x)(-) reduction during dialysis reflects an increase in NO release induced by EA stimulation in acupoint and that cGMP mediates the signaling functions of NO to improve local microcirculation, which, at least in part, contributes to the effects of acupuncture.
Microcirculation (New York, N.Y.: 1994) 08/2009; 16(5):434-43. · 2.37 Impact Factor
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ABSTRACT: Most acupuncture points correspond to low skin-resistance points (LSRP) on the body surface along the meridians. We did three experiments which conformed that the skin nitric oxide (NO) concentration and expression of neuronal nitric oxide synthesis (nNOS) were higher than those in non-acupoints, and non-meridian control points. Noradrenaline (NE) synthesis/release was modulated by exogenous NO donor and selective inhibitor of nNOS in the skin acupoints/meridians. Skin electrical currents in low skin resistance points were modified by L-arginine-derived NO synthesis and NE. As a conclusion, NO-NE contribute to low resistance characteristics of acupoints and meridians.
Zhen ci yan jiu = Acupuncture research / [Zhongguo yi xue ke xue yuan Yi xue qing bao yan jiu suo bian ji] 07/2008; 33(3):213-6.
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ABSTRACT: The effects of nitric oxide (NO) and noradrenergic activation in the posterior hypothalamus on arterial pressure tolerance induced by subcutaneous injection of nitroglycerin (NTG) was investigated in anesthetized Sprague-Dawley rats. Intravenous injections of NTG (3, 10, and 30 microg/kg) and sodium nitroprusside (1, 3, and 10 microg/kg) produced dose-dependant decreases in arterial blood pressure. Tolerance to NTG was produced by subcutaneous administration of 4.0 mg of NTG as 4 separate hourly injections of 1.0 mg each, affecting the dose-dependent response of NTG IV injection. The 4 high-dose NTG pulse injections produced a marked shift in the dose-response curves for arterial pressure depression induced by intravenous injection of the challenge doses of NTG, but did not alter hypotensive responses to sodium nitroprusside. The tolerance responses to arterial pressure depression were enhanced by a bilateral microinjection of NTG (1 nmol) and by diethylamine NONOate (1 nmol), an NO donor, into the posterior hypothalamus. Bilateral microinjection of guanethidine (1.5 nmol), a noradrenergic blocker, into the posterior hypothalamus inhibits NTG tolerance in a period of time within 2 hours. We conclude that exogenous NO and noradrenergic activation in the posterior hypothalamus play an important role in arterial pressure tolerance to systemically administered NTG.
Journal of Cardiovascular Pharmacology and Therapeutics 07/2008; 13(2):98-106. · 1.75 Impact Factor
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Sheng-xing Ma
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ABSTRACT: We have found that nitric oxide (NO) contents are increased in skin acupoints associated with enhanced neuronal NO synthase (nNOS) protein level in rats. Our recent studies show that L-arginine-derived NO synthesis increases skin electric currents over acupoints in rats. Consistently, norepinephrine (NE) turnover rate is decreased in acupoints with high skin electric currents, and enhanced 3H-NE synthesis/release in acupoints/meridians is facilitated by presence of an exogenous NO donor and inhibited by an inhibitor of NO synthesis. We have developed an innovative method to collect and measure NO metabolites from acupoints and meridians on the skin surface in humans. NO contents are consistently increased over PC and BL acupoints in humans, and increased NO content is reduced by anti-bacteria on skin surface. We conclude that the nonenzymatic reduction of nitrate by bacteria is involved in chemical generation of NO on skin acupoints/meridians in addition to neuronal NOergic system. NO mediates noradrenergic function on skin sympathetic nerve activation, which contributes to low resistance characteristics of acupoints and meridians.
Zhen ci yan jiu = Acupuncture research / [Zhongguo yi xue ke xue yuan Yi xue qing bao yan jiu suo bian ji] 03/2008; 33(1):47-8.
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ABSTRACT: The present study quantified total nitrate and nitrite (NOx-) collected from the skin surface along acupuncture points (acupoints) and determined whether non-enzymatic reduction of nitrate by bacteria is involved in chemical generation of nitric oxide (NO) on acupoints. A small plastic tube (0.5 x 7 cm) cut in half lengthwise was taped to the forearm or leg in 50 healthy volunteers. NO-collecting solutions with NO-scavenging compounds, hemoglobin or 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide, was placed inside the tubing attached to the skin surface for 20 min. The concentrations of NOx- in the collected samples were quantified by using chemiluminescence. NOx- concentration was significantly enhanced in four acupoints on the pericardium meridian and in two acupoints on the bladder meridian compared with those collected on non-meridian control areas. The time intervals of NOx- levels were significantly higher at the first 20 min of acupoint collection, but the concentrations were similar among the study groups collected at 20-40, 40-60, and 60-80 min. NOx- concentrations and numbers of bacteria colonies detected on the skin surface were markedly reduced by pretreatment of skin with sodium hypochlorite compared to water treatment. This is the first evidence showing that NO has been successfully quantified on skin acupoints by a non-invasive device in humans. We conclude that NO is physiologically released from the skin surface with a higher level at acupoints, and that the non-enzymatic reduction of nitrate by bacteria is involved in chemical generation of NO on skin acupoints in addition to l-arginine-derived NO synthesis.
Nitric Oxide 10/2007; 17(2):60-8. · 3.55 Impact Factor
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ABSTRACT: 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.
Life Sciences 12/2006; 79(23):2157-64. · 2.53 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
The Journal of Alternative and Complementary Medicine 06/2005; 11(3):423-31. · 1.59 Impact Factor
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ABSTRACT: 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.
Brain Research 03/2005; 1037(1-2):70-7. · 2.73 Impact Factor
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Sheng-Xing Ma
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ABSTRACT: 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.
Evidence-based Complementary and Alternative Medicine 07/2004; 1(1):41-47. · 4.77 Impact Factor
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ABSTRACT: 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.
Journal of Neurophysiology 09/2003; 90(2):780-5. · 3.32 Impact Factor
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ABSTRACT: 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.
European Journal of Pharmacology 08/2003; 472(3):179-87. · 2.52 Impact Factor
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ABSTRACT: 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.
AJP Heart and Circulatory Physiology 05/2003; 284(4):H1057-63. · 3.71 Impact Factor
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Sheng-Xing Ma
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ABSTRACT: 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.
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.
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.
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.
The Journal of Alternative and Complementary Medicine 04/2003; 9(2):207-15. · 1.59 Impact Factor
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ABSTRACT: 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.
AJP Regulatory Integrative and Comparative Physiology 05/2002; 282(5):R1521-7. · 3.34 Impact Factor
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ABSTRACT: 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 & electro-therapeutics research 01/2002; 27(3-4):157-69. · 1.30 Impact Factor
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ABSTRACT: Transition from fetal to newborn life is accompanied by a marked rise in circulating norepinephrine (NE) concentrations though arterial blood pressure does not substantively change. Nitric oxide (NO) plays an important role in the central regulation of sympathetic tone in the nucleus tractus solitarius (NTS) and neuronal NO synthase (nNOS) expression is functionally regulated in the brain. The purpose of these studies was to determine the influence of transition at birth on nNOS expression in the brainstem nuclei, particularly in the NTS, associated with changes in arterial pressure and plasma NE concentration. Experiments were performed using time-dated gestational ewes with twin fetuses. Arterial blood pressure was recorded and arterial blood NE concentrations were measured in the term fetus (gestational 147–148 days) and newborn lambs (4 h of postnatal age). The fetal and newborn animals were then perfused with 4% paraformaldehyde. Sections of the medulla were examined by using both immunolabeling with a polyclonal antibody directed against nNOS and nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry, a marker for expression of nNOS. Micrographs were quantified using a microscope with reticule grid to measure the number of positive cells containing color staining in the brainstem nuclei. Plasma NE concentration in the newborn was more than two-fold greater compared to fetal values but mean arterial blood pressure was similar between fetus and newborn. The nNOS positive cells and NADPHd positive cells were significantly increased in the medial NTS (mNTS) of the newborn compared to fetus. nNOS immunoreactivity and NADPHd reactivity tended to increase in the rostral ventral medulla (RVM) in newborn, but were not altered in other brainstem nuclei during the transition from fetal to newborn life. The results suggest that nNOS expression in the mNTS is predominately enhanced at 4 h of neonatal age vs. the term fetus. We conclude that elevated circulating NE is associated with up-regulation of nNOS in the mNTS which may serve a protective role in central regulation of neonatal arterial blood pressure.
Developmental Brain Research.
