• Herbal Formula Science
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• v.17 no.2
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• pp.143-150
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• 2009

The effects of aqueous extract of Schizandrae Fructus (AESC) on lead (Pb)-induced changes of monoamine neurotransmitters in the hippocampus (HIP) of adult rats were investigated. Male Sprague-Dawley rats were received intraperitoneal (i.p.) administration of Pb acetate (5 mg/kg/d) for 28 days and sacrificed 7 days after the last administration. Concentrations of norepinephrine (NE), dopamine (DA), serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA) in HIP were measured by HPLC. There were significant decreases of NE, DA, 5-HT and 5-HIAA in Pb treated rats (P < 0.05), while pretreatment with AESC (100 mg/kg/d or 300 mg/kg/d, p.o., 2 h before Pb) greatly inhibited the decrease of monoamine transmitters, respectively (P < 0.05). Also, AESC (300 mg/kg/d) significantly increased the reduction of glutathione contents and superoxide dismutase activities in HIP induced by chronic Pb. These results suggest that AESC ameliorates Pb-induced depletion of monoamine neurotransmitters in HIP through its antioxidant activity.

• YAKHAK HOEJI
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• v.35 no.5
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• pp.394-400
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• 1991

A question whether abnormal responsiveness of hypothalamic catecholaminergic nervous system to ovarian steoid hormones in spontaneously hypertensive rats (SHR) exist was investigated. Four groups of experimental animals were prepared for SHR and normotensive Wistar rats (NW) respectively: 1) intact, 2) ovariectomized (OVX+V), 3) ovariectomized and estrogen treated (OVX+E), 4) ovariectomized and estrogen plus progesterone treated (OVX+E+P) groups. Hypothalami from experimental animals were dissected out and used for determination of .alpha.-adrenergic receptor binding characteristics and catecholamine contents. Norepinephrine(NE) content and B$_{max}$ of $\alpha_1$-adrenergic receptors in hypothalami were greater in intact SHR than in intact NW, but dopamine(DA) content was lower in SHR than in NW. Neither contents of NE and DA nor binding characteristics of $\alpha_1$-adrenergic receptors were different in OVX+V and OVX+E group from intact group of both SHR and NW. Kd and B$_{max}$ of $\alpha_1$-adrenergic receptors in OVX+E+P was lower than that in intact SHR but not in NW. DA content was lower in OVX+E+P than in intact group of SHR and NW. The result of the present study indicates that there is an abnormal responsiveness of hypothalamic catecholaminergic nervous system to ovarian steroid hormones in SHR which may be one of genetically-determined factors probably not responsible for the development of hypertension.

• Korean Journal of Acupuncture
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• v.34 no.1
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• pp.37-46
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• 2017

Objectives : The acupuncture about acupoint affects the production of NO, NOS, and NE.Local action of acupuncture is important for acupuncture treatment. To prove this, the revelation degree of NO, NOS, and NE was observed by stimulating the acupuncture at the connecting point of SP4, KI4, and LR5 in the depths of Superficial layer, Middle layer and Deep layer. Methods : Needles were inserted into rats, on each right and left sides of the connecting point, SP4, KI4 and LR5 acupoints which are the stream points of the foot meridian. After insertion, needles were retained for three minutes. After the retention, rat was sacrificed via cardiac puncture, and tissues of each SP4, KI4 and LR5 point near meridian vessel was extracted to examine the changes in the expression of NO, NOS and NE. Results : In terms of the effect in NO production, there was significant increase in the Superficial layer, Middle layer and Deep layer at KI4. In terms of the effect in NE production, there was significant decrease in the Superficial layer at SP4 and increase in the Superficial layer, Middle layer and Deep layer at LR5. In terms of the effect in nNOS production, there was significant increase in the Superficial layer, Middle layer and Deep layer at SP4 also in the Superficial layer at KI4. In terms of the effect in eNOS production, there was a significant increase in the Superficial layer, Middle layer and Deep layer at SP4, KI4 and LR5. In terms of the effect in iNOS production, there was significant increase in the Superficial layer, Middle layer and Deep layer at SP4, KI4 and LR5. Conclusions : The effect of acupuncture applied at the connecting point of six meridians of the foot on the activities of NO, NOS and NE could be observed, and it can be induced from the effect of needle stimulation on disrupted local and systemic nervous responses.

• Journal of Yeungnam Medical Science
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• v.9 no.2
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• pp.382-395
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• 1992

GABA is an inhibitory neurotransmitter in central nervous system and produce sedative, antianxiety and muscle reaxing effects via $GABA_A$ receptor or $GABA_B$ receptor. Recently it is known that GABA is widely distributed throughout peripheral organs and may playa physiological role in certain organ. The vas deferens is innervated by species-difference. These study, therefore, was performed to investigate the mode and the mechanism of action of GABA on the norepiniphrine-, ATP- and electric stimulation-induced contraction of vas deferens of rat. Sprague-Dawley rats were sacrificed by cervical dislocation. The smooth muscle strips were isolated from the prostastic portion and were mounted in the isolated muscle bath. PSS in the bath was aerated with 95/5%-$O_2/CO_2$ at $33^{\circ}C$. Muscle tensions were measured by isometric tension transducer and were recorded by biological recording system. 1. GABA, muscimol, a $GAB_A$ agonist, and baclofen, a $GABA_B$ agonist inhibited the electric field stimulation(EFS, 0.2Hz, 1mSec, 80 V, monophasic square wave)-induced contraction with a rank order of potency of GABA greater than baclofen greater than muscimol. 2. The inhibitory effect of GABA was antagonized by delta aminovaleric acid(DAVA), a $GABA_B$ antagonist, but not by bicuculline, a $GABA_A$ mtagonist. 3. The inhibitory effect of baclofen was antagonized by DAVA, but the effect of muscimol was not antagonized by bicuculline. 4. Exogenous norepinephrine(NE) and ATP contracted muscle strip concentration dependently, but the effect of acetylcholine was negligible : and GABA did not affect the NE-and ATP-induced contractions. 5. GABA, baclofen and muscimol did not affect basal tone, and GABA did not affect the NE-and ATP-induced contractionsm 6. EFS-induced contraction was including 2 distinctable components. The first phasic component was inhibited by beta gamma-methylene ATP(mATP), a desensitizing agent of APT receptor and the second tonic component was reduced by pretreatment of reserpine(3 mg/Kg, IP). 7. GABA inhibited the EFS-induced contraction of reserpinized strips, but not the mATP-treated strips. These results suggest that in the prostatic portion of the rat vas deferens, adrenergic and purinergic neurotransmissions are exist, and GABA inhibits the release of ATP via presynaptic $GABA_B$ receptor on the excitatory neurons.

• The Korean Journal of Pharmacology
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• v.22 no.2
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• pp.79-87
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• 1986

Recently it has been shown that central dopaminergic system regulates the renal function and that intracerebroventricularly (icv) administered dopamine (DA) produces antidiuresis and antinaturiuresis, resembling icv norepinephrine, and evidence has been accumulated which would suggest the involvement of adrenergic system in the DA effects. It was attempted therefore in this study to see whether the DA effect is influenced by pretreatment of yohimbine which is known as a specific ${\alpha}_2-adrenoceptor$ antagonist. Yohimbine produced, when given icv in doses of $100\;{\mu}g/kg$, marked antidiuresis and antinatriuresis along with decreases in renal perfusion and glomerular filtration. DA, in doses of $15\;{\mu}g/kg$, also produced antidiuresis and antinaturiuresis. However, after yohimbine-pretreatment DA $15\;{\mu}g/kg$ improved renal hemodynamics, and electrolyte excretion and urine flow rate transiently increased. With $150\;{\mu}g/kg$ DA, the antidiuresis was more marked in the control group. But the yohimbine-pretreated animals responded with marked diuresis and natriuresis, sodium excretion increasing more than three-fold, which lasted for 20 minutes. $K^+-excretion$, osmolar clearance as well as free-water reabsorption increased. Renal hemodynamics improved partly. Apomorphine, a DA agonist, when given icv in doses of $150\;{\mu}g/kg$, produced diuresis and naturiuresis, concomitant with increased renal hemodynamics. Yohimbine-pretreatment however did not abolish the apomorphine-induced diuresis and naturiuresis. Antidiuresis and antinatriuresis elicited by norepinephrine, $10\;{\mu}g/kg$, was not affected by yohimbine-pretreatment. These results indicate that the renal effects of icv DA is not so simple as those of norepinephrine, and the diuretic natriuretic cffect which had been masked by the hemodynamic effect becomes manifest only when the decreases in hemodynamics were removed by the pretreatment of yohimbine. It was further suggested that those DA receptors which mediate the natriuretic response to icv DA is not affected by yohimbine, whereas those receptors involved in the decrease in renal hemodvnamics are blocked by yohimbine. And the possibility of involvement of adrcnergic system in the DA action is not substantiated.

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.600-612
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• 1996

Background : Recent studies deported that untreated patients with obstructive sleep apnea syndrome had high long-term mortality rates, and cardiovascular complications of these patients clad a major effect on mortality. Several data indicates that obstructive sheep apnea syndrome contributes to the development of diurnal systemic hypertension. But the pathophysiological mechanism of the development of systemic hypertension in these patients is still uncertain. This study was performed to evaluate the possible role of sympathetic nervous system activity for the development of systemic hypertension in patients with obstructive sleep apnea syndrome. Method : 35 patients with obstructive sleep apnea syndrome(OSAS) and 13 Control subjects(control) were included in this study. 21 patients of OSAS were normotensives(OSAS-NBP), and 14 patients of OSAS were hypertensives(OSAS-HBP). Full night polysomnography was undertaken to all subjects. We measured plasma norepinephrine(NE) and epinephrine(EP) concentrations during waking and sleep, using high performance liquid chromatography, in all patients and control subjects. Results : In OSAS, OSAS-NBP and control, plasma NE and EP concentrations during sleep were lowed than during waking(p<0.01). But, in OSAS-HBP, these was no difference between during waking and sleep. Plasma NE concentrations during sleep of OSAS, OSAS-NBP and OSAS-HBP were higher than Control(p<0.05). In OSAS-HBP, daytime systolic blood pressure correlated with plasma NE concentration during sleep(r=0.7415, p<0.01), arid correlated inversely with mean arterial oxygen saturation(r=-0.6465, p<0.05) or arterial oxygen saturation nadir(r=-0.6) 14, p<0.05) during sleep. Conclusion : The sympathetic activity during sleep of obstructive sleep apnea syndrome patients was higher than control subjects. In obstructive sleep apnea syndrome patients with systemic hypertension, there was no diurnal variation of sympathetic activity, and there was correlation between daytime systolic blood pressure and sympathetic activity during sleep. These data suggests that chronic hyperactivity of sympathetic nervous system may contribute to the development of diurnal systemic hypertension in patients with obstructive sleep apnea syndrome.

• Korean Journal of Ichthyology
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• v.12 no.1
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• pp.38-45
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• 2000

Depending on the fish species the vascular tone is distinctively regulated by numerous vasoactive substances. In most fish species the regulatory role of autonomic neurotransmitters and other vasoactive substances are not well defined. This research was designed to delineate the regulatory role of various endogenous autonomic neurotransmitters known to be important in mammalian vascular systems on isolated Israeli carp ventral aorta. Acetylcholine(ACh) contracted the aorta regardless of the pre-existing level of vascular tone, and the contraction was almost completely abolished by a cholinergic-muscarinic antagonist atropine. Endogenous, multiple receptor ($\alpha$ and $\beta$)-acting adrenergic agonist epinephrine (Epi) relaxed the vessel in the presence and absence of the pre-existing tones. Another endogenous multiple receptoracting agonist norepinephrine (NE) weakly contracted the aorta in non-preconstrcted state, but the response was reversed to relaxation when preconstricted. Isoproterenol, ${\alpha}\;{\beta}$ adrenergic receptor agonist, was a potent vasodilator whereas an ${\alpha}_1$ agonist phenyephrine was a contractor. The ${\alpha}_2$ adrenergic receptor agonist clonidine has not any significant effect in altering the vascular tone. The vasorelaxing action of Epi, NE and isoproterenol was significantly attenuated by $\beta$ receptor antagonist propranolol. These results imply that ACh may primarily play a contractor role via muscarinic receptor activation while adrenergic agonists, Epi and NE, are relaxants through activation of $\beta$ adrenergic receptors in vivo.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.3
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• pp.593-599
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• 2008

This research was aimed to examine the effect of Polygoni Multiflori Radix extract on the blood pressure in spontaneous hypertensive rat (SHR) and norepinephrine - induced arterial contraction in rabbit. In order to investigate the effect of Polygoni Multiflori Radix on rabbit's contracted vascular ring detached from common carotid artery, vascular ring with intact or damaged endothelium was used for the experiment using organ bath. To analyze the mechanism of Polygoni Multiflori Radix-induced relaxation, Polygoni Multiflori Radix extract was infused into contracted vascular ring which had been pretreated by $N{\omega}$-nitro-L-arginine(L-NNA), Methylene blue(MB), and $Ca^{2+}$ was infused into contracted vascular ring induced by NE after treatment of Polygoni Multiflori Radix extract in $Ca^{2+}$-free solution. The results were as follows: Systolic blood pressure was significantly attenuated by administration of Polygoni Multiflori Radix. Blood flow and aldosterone were significantly decreased, but velocity and renin were not affected by Polygoni Multiflori Radix. Polygoni Multiflori Radix had an effective relaxation to the contracted vascular ring by NE in 0.03 mg/ml, 0.1 mg/ml and 0.3 mg/ml level. Polygoni Multiflori Radix had an effective relaxation to the intact endothelium vascular ring, but when endothelium was removed, vascular ring did not relax. Polygoni Multiflori Radix-induced relaxation was inhibited by the pretreatment of L-NNA and MB. Pretreatment of Polygoni Multiflori Radix extract inhibit the contraction by influx of extra-$Ca^{2+}$ in contracted vascular ring induced by NE in $Ca^{2+}$-free solution. As mentioned above, we suggest that Polygoni Multiflori Radix relaxes vascular ring through suppress influx of extra-cellular $Ca^{2+}$ by the action of nitric oxide from endothelium.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.3
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• pp.666-671
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• 2008

This study was undertaken to define the effect of ChungGongGo extract on norepinephrine-induced arterial contraction in rabbit. In order to investigate the effect of ChungGongGo extract on rabbit's contracted vascular ring detached from common carotid artery, vascular ring with intact or damaged endothelium was used for the experiment using organ bath. To analyze the mechanism of ChungGongGo extract-induced relaxation, ChungGongGo extract was infused into contracted vascular ring which had been pretreated by $N{\omega}$-nitro-L-arginine(L-NNA), Methylene blue(MB), and $Ca^{2+}$ was infused into contracted vascular ring induced by NE or KCl after treatment of ChungGongGo in $Ca^{2+}$-free solution. The results were as follows: ChungGongGo extract had an effective relaxation to the contracted vascular ring by NE in 1.0mg/ml and 0mg/ml level. ChungGongGo extract had an effective relaxation to the intact endothelium vascular ring, but when endothelium was removed, vascular ring did not relax. ChungGongGo extract-induced relaxation was inhibited by the pretreatment of L-NNA and MB. Pretreatment of ChungGongGo extract inhibit the contraction by influx of extra-$Ca^{2+}$ in contracted vascular ring induced by NE in $Ca^{2+}$-free solution. As mentioned above, we suggest that ChungGongGo relaxes vascular ring through suppress influx of extra-cellular $Ca^{2+}$ by the action of nitric oxide from endothelium.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.156-156
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• 1993

본 연구에서는 생체 뇌 국소부위의 세포외액을 대상으로 실험할 수 있는 뇌 미세투석법을 이용하여 후시상하부에서 유리되는 monoamine의 세포외액 농도에 대한 전신 혈압변화의 영향을 관찰함으로써, 심혈관 조절에 대한 후시상하부의 monoamine성 뉴론의 생리적 역할을 규명하고자 하였다. 마취한 흰쥐의 머리를 뇌정위 고정장치에 고정시키고 미세투석관 (microdialysis probe)을 후시상하부에 위치시킨 후 링거액으로 관류하였다. 미세투석액내에 존재하는 monoamine성 신경 전달물질들과 그 대사체들의 정량분석은 고속액체크로마토그라피와 전기화학검출기를 이용하여 실시하였다. 전신 혈압을 40분 동안 약 40mmHg 상승 혹은 30mmHg 감소시키기 위하여 L-phenylephrine hydrochloride (800ng/100 g/min) 혹은 nitroprusside dihydrate (500 ng/100 g/min)를 대퇴정맥을 통하여 주사하였다. 후시상하부로 부터 20분 간격으로 얻은 투석액에서 신정화학물질들의 농도는 미세투석관 삽입후 2시간에 안정되었다. 관류액의 $K^{＋}$ 농도를 90 mM로 증가시켰을 때 후시상하부의 투석액에서 norepinephrine (NE) 과 serotonin (5-HT)의 농도는 각각 기준치의 176.5 $\pm$ 14.8%, 149.1 $\pm$ 2.3%로 증가하였다. Phenylephrine (i.v.)으로 유발된 전신 혈압상승에 의하여 NE과 5-HT의 양은 각각 기준치의 79.3 $\pm$ 4.4%, 61.4 $\pm$ 10.3%로 유의하게 감소하였다. 또한 nitroprusside (i.v.)에 의하여 전신혈압이 감소하였을 때 투석액내 5-HT의 양은 기준치의 195.0 $\pm$ 23.0% 로 유의하게 증가하였다. 후시상하부의 투석액내 monoamine성 대사체들의 경우에는 전신 혈압의 변화에 대한 유의한 반응을 나타내지 않았다. 이상을 종합하면 전신 혈압이 증가되었을 때는 말초 압수용체의 흥분에서 기시한 신경충동이 후시상하부에 전달되어 신경말단에서 5-HT 과 NE 의 유리가 감소되고, 5-HT의 경우에는 전신 혈압이 감소되었을때 그 반대 현상이 일어난다는 가설을 제시할 수 있다. 본 연구의 결과는 생체상태에서 혈압변화에 대한 후시상하부의 monoamine성 조절양상을 규명한 것으로서 특히 후시상하부의 serotonin성 신경계를 통한 심혈관 중추조절의 가능성을 처음으로 제시한 것이다.