• 대한수의학회지
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• 제45권4호
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• pp.485-493
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• 2005

We studied the effects of trazodone on arterial blood pressure in anesthesized guinea pigs, and on vascular responses in isolated thoracic aorta. Trazodone produced a concentration-dependent relaxation in phenylephrine-precontracted endothelium intact (+E) rings, but not in a KCl-precontracted aortic rings. These relaxant effects of trazodone on +E rings were significantly greater than those on denuded (-E) rings. The trazodone-induced relaxation was suppressed by glibenclamide and tetrabutylammonium, but not by N(G)-nitro-L-arginine (L-NNA), N(omega)-nitro-L-arginine methyl ester (L-NAME), methylene blue (MB), nifedipine, indomethacin, 2-nitro-4-carboxyphenyl-n,n-diphenylcarbamate (NCDC) and clotrimazole. In vivo, infusion of trazodone elicited a significant decrease in arterial blood pressure. Trazodone-induced blood pressure lowering was markedly inhibited by intravenous pretreatment of prazosin but not by pretreatment of saponin, L-NNA, L-NAME, MB, nifedipine, glibenclamide, clotrimazole and NCDC. In addition, trazodone produced an increase in twitch force of isolated papillary muscle and left ventricular pressure of perfused heart. These findings suggest that the endothelium-independent vasorelaxant effect of trazodone may be explained by activation of $Ca^{2+}$-activated and ATP-sensitive $K^+$ channels, and the hypotensive effect of trazodone is not associated with cardiac contraction.

• The Korean Journal of Physiology and Pharmacology
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• 제20권6호
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• pp.605-611
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• 2016

Ketamine is an anesthetic with hypertensive effects, which make it useful for patients at risk of shock. However, previous ex vivo studies reported vasodilatory actions of ketamine in isolated arteries. In this study, we reexamined the effects of ketamine on arterial tones in the presence and absence of physiological concentrations of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) by measuring the isometric tension of endothelium-denuded rat mesenteric arterial rings. Ketamine little affected the resting tone of control mesenteric arterial rings, but, in the presence of 5-HT (100~200 nM), ketamine ($10{\sim}100{\mu}M$) markedly contracted the arterial rings. Ketamine did not contract arterial rings in the presence of NE (10 nM), indicating that the vasoconstrictive action of ketamine is 5-HT-dependent. The concentration-response curves (CRCs) of 5-HT were clearly shifted to the left in the presence of ketamine ($30{\mu}M$), whereas the CRCs of NE were little affected by ketamine. The left shift of the 5-HT CRCs caused by ketamine was reversed with ketanserin, a competitive 5-$HT_{2A}$ receptor inhibitor, indicating that ketamine facilitated the activation of 5-$HT_{2A}$ receptors. Anpirtoline and BW723C86, selective agonists of 5-$HT_{1B}$ and 5-$HT_{2B}$ receptors, respectively, did not contract arterial rings in the absence or presence of ketamine. These results indicate that ketamine specifically enhances 5-$HT_{2A}$ receptor-mediated vasoconstriction and that it is vasoconstrictive in a clinical setting. The facilitative action of ketamine on 5-$HT_{2A}$ receptors should be considered in ketamine-induced hypertension as well as in the pathogenesis of diseases such as schizophrenia, wherein experimental animal models are frequently generated using ketamine.

• The Korean Journal of Physiology
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• 제22권2호
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• pp.231-243
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• 1988

This study was performed to investigate the mechanism of changes in arterial blood pressure, as a typical example of somatosympathetic reflex, induced by activation of muscular afferent nerves. Cats were anesthetized with ${\alpha}-chloraloae$ (60 mg/kg, i.p.). Afferent fibers in muscle nerve were activated by various method muscle contraction, electrical stimulation of muscle nerves, intraarterial injection of some algesic substances and noxious mechanical stimulation etc-and the evoked changes in arterial blood pressure were monitored. The effects of intravenous or direct spinal administration of morphine on the changes in arterial blood pressure induced by activation of the muscle afferent fibers were observed and also the effects of spinal lesions made in the $L1{\sim}L3$ spinal cord on them were studied to identify the ascending spinal pathways of the somatosympathetic reflexes. Followings are the results obtained. 1) The stimulation of medial gastrocnemius nerve under non-paralyzed condition with C-strength, low frequency (lower than 20 Hz) stimuli elicited a depressor response and a pressor response was elicited with C-strength, high frequency stimuli, of which the maximal response was observed at 100 Hz stimulation. 2) When the animal was paralyzed, depressor response to stimulation of the medial gastrocnemius nerve was observed with C-strength, $0.5{\sim}5Hz$ stimuli although the amplitude of the depressor response was decreased. The maximal pressor response was observed during stimulation with C-strength, $20{\sim}100Hz$ stimuli. 3) Intraarterial injection of some algesic substances induced marked pressor responses while noxious mechanical stimulation of the medial gastrocnemius muscle was not enough to elicit any significant changes (larger than 10 mmHg) in arterial blood pressure. 4) Systemically administered morphine (2 mg/kg) lowered the arterial blood pressure immediately and persistently and it was reversed by administration of naloxone. Direct spinally administered morphine did not elicit any changes. 5) The pressor response elicited by the activation of muscle afferent nerves was strengthened by systemic morphine administration while the depressor response tended to decrease. 6) Morphine administered on the spinal cord directly, decreased pressor response but did not change depressor response. From the above results it is concluded that there are separate groups of afferent nerves in the medial gastrocnemius nerve, which elicit pressor and depressor responses and the spinal ascending pathways of them are also separated from each other.

• The Korean Journal of Physiology
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• 제26권2호
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• pp.123-128
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• 1992

The present study was undertaken to examine if endogenous nitric oxide is partly responsible for the high calcium induced vasorelaxation in vitro. Isolated porcine coronary arterial rings were suspended in the tissue chamber and their changes in isometric tension were recorded. KCI little affected the vascular tension in the calcium free media, but subsequent addition of cumulative doses of $CaCl_3$ from 1 to 40 mM caused a contraction followed by complete relaxation. The maximum tension was noted at the calcium concentration in the media of 5 mM, and then the tension progressively declined at 10-40 mM. The relaxation was slightly attenuated in the endothelium-denuded preparation. The relaxation was converted into a contraction by the addition of methylene blue. The relaxation response was not affected in the presence of indomethacin, but was significantly attenuated by $N^w-nitro-L-arginine$ methyl ester pretreatment. These results suggest that the calcium induced vasorelaxation is in part attributable to the release of endogenous nitric oxide.

• 동아시아식생활학회지
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• 제15권5
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• pp.606-612
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• 2005

This study was performed to provide basic data that predict the application of Saengmaegsan(SMS) as medicinal food. SMS has been used in oriental medicine for many years as a therapeutic agent for cerebral disease. We examined the effects of SMS on physiological function in isolated abdominal aorta and femoral artery from rabbit and measured the changes of regional cerebral hood flow(rCBF), which was continually monitored by laser-doppler flowmeter and pressure transducer in anesthetized adult Spargue-Dawley rats through the data acquisition system composed of MacLab and Macintosh computer. The contraction forces by injection of norephinephrine in isolated abdominal aorta and femoral artery were significantly decreased in each concentration of SMS treatment compared with control. rCBF was increased by SMS in a dose-dependent manner. These results suggest that SMS causes a diverse response of rCBF and arterial diameter. These mechanism in rCBF increase may be mediated by prostaglandis, cyclic GMP and adrenergic $\beta-receptor$. Also mechanism in artery contraction decrease is also mediated by prostaglandis and cyclic GMP. These results indicate that SMS can be nsed as a safe and clinically applicable as a supplementation of diet therapy for cerebral cardiovascular disease patients.

• 대한한방내과학회지
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• 제24권2호
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• pp.260-268
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• 2003

Object : This study was undertaken to define the mechanism of GwakHyangJungGiSan-induced relaxation in rabbit common carotid artery contracted by agonists. Method : In order to investigate the effect of GwakHyangJungGiSan on rabbit's contracted vascular ring detached from common carotid artery, vascular ring intact or damaged endothelium was used for the experiment using organ bath. To analyze the mechanism of GwakHyangJungGiSan-induced relaxation, GwakHyangJungGiSan extract was infused into contracted vascular ring which had been pretreated by pretreatment of indomethacin(IM), tetraethylammonium chloride(TEA), $N{\omega}-nitro-L-arginine(L-NNA)$. Result : GwakHyangJungGiSan blocks an inflow of $Ca^{2+}$ and relaxes vascular ring by the action of Nitric oxide from endothelium. Consequently when GwakHyangJungGiSan is prescribed, a rise in blood pressure by the resistance of peripheral vessel may be controlled to some extent and so it is anticipated that hypertension, a disorder of blood flow from the vascular contraction and vascular disease will be treated well.

• 생명과학회지
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• 제13권5호
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• pp.634-641
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• 2003

외부에서 가해진 비소 스트레스가 내피유무에 따른 흰쥐 대동맥의 수축력 증가와 이완반응에 미치는 영향을 알아보고자 본 실험을 실시하였다. 혈압의 측정은 생리기록계를 이용하였고, 내피 유무에 따른 혈관의 수축력은 Organ bath에 조직을 걸고 자동조절 생리기록계를 이용하여 측정하였다. 중추신경계를 파괴시킨 흰쥐의 생체 내 실험에서 비소처리로 vasopressin과 phenylephrine에 의한 혈관 수축력은 대조군에 비해 각각 19.1%와 46.6%로 대동맥의 혈압은 상승되었다. 0, 0.5, 1, 2 및 4 mM As을 처리한 적출 대동맥 실험에서 phenylephrine $(10^{-6}M)$을 가했을 때 5시간까지는 혈관 수축력의 변화가 미미했으나 8시간째 비소 처리군은 대조군에 비해 39% 증가된 값을 보여 수축력이 더욱 유의하게 증가되었다. 내피 제거 시 저농도 비소처리에서 다소 신속한 수축반응을 보였으나 고농도 비소 처리시에는 내피유무에 따른 차이가 유의적이지 않았다. 이완제 sodium nitroprusside와 acetylcoline를 처리했을 때 대조군에 비해 다소 증가된 이완력을 보였고, 시간경과에 따라 내피 비의존적인 nitroprusside와 달리 내피 의존적인 acetylcholine에서 이완력이 대조군에 비해 다소 촉진되었다. 이상의 결과에서 4 mM As처리시 혈관의 수축력은 증가되었으나 내피유무에 따른 차이는 유의적이지 않았고, 내피가 혈관의 이완력을 다소 촉진시킨 것으로 나타났다. 결론적으로 비소처리한 혈관은 내피유무와 무관하게 수축력이 증가되어 장기간 고농도 비소에 노출 시 고혈압을 유발할 우려가 있을 것으로 여겨진다.

• 대한한방내과학회지
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• 제24권2호
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• pp.220-232
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• 2003

Objective : The purpose of this study was to analyze the effects of HwangRyunHaeDok-Tang and combinations of constituent herbs on the arterial contraction. Methods : In order to investigate the effects Scutellariae Radix. Coptidis Rhizoma, Phellodendri Cortex and Gardeniae Fructus, in which one of them, two of them, and all of them, were used to exam. Results : The results were summarized as follows; 1. HwangRyunHaeDok-Tang significantly inhibited the contraction of artery induced by Norepinephrine(NE). However the atonic effect was slightly blunted when the vascular endothelial cell was removed. No significant change in the atonic effect of HwangRyunHaeDok-Tang was found when $_L-NNA$ was used as a preliminary treatment. These results indicate that the vascular atonic effect by HwangRyunHaeDok-Tang is slightly dependent on the endothelial cell, and that the HwangRyunHaeDok-Tang works directly to the vascular smooth muscle in creating the vascular atonic effect. 2. The pretreatment of HwangRyunHaeDok-Tang extract significantly inhibited the contractile response to additive application of $Ca^{2+}$ in the strips which were contracted by NE in $Ca^{2+}$-free solution. 3. HwangRyunHaeDok-Tang extract increased the contraction of arterial smooth muscle induced by KCl. Therefore, it can be concluded that HwangRyunHaeDok-Tang may block the NE-receptor or receptor-operated $Ca^{2+}$ channel. 4. It was determined that Scutellariae Radix, Coptidis Rhizoma and Phellodendri Cortex among the ingredients of HwangRyunHaeDok-Tang have a vascular atonic effect. In addition, those ingredients plays a role in strengthening the atonic effect by working with other herbal medicines. Gardeniae Fructus causes the blood vessel to contract. but it does not influence the atonic effects of other herbal medicines. However Gardeniae Fructus tends to inhibit the vascular atonic effect of Phellodendri Cortex. Conclusion : Based on the above results, it can be said that HwangRyunHaeDok-Tang can be applied to cure hypertension considering those three herbs have significant effects of relaxation.

• Journal of Yeungnam Medical Science
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• 제23권1호
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• pp.36-44
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• 2006

진통과 해열작용을 가진 NSAIDs는 소화기계에 대한 부작용 때문에 COX-2 선택성 억제제로 대체되고 있다. 그러나 COX-2 선택적 억제제는 심혈관계에 대한 부작용이 보고되고 있어 혈관 평활근에 대한 직접적인 연구가 필요하다. 이에 본 연구에서는 혈관 반응성에 미치는 celecoxib와 aspirin, indomethacin의 영향을 비교 분석하였다. 또한 COX-1, COX-2 단백질 발현에 대한 indomethacin과 NO 공여제의 영향을 조사하였다. Phenylephrine 유발 수축반응에서 전처치 된celecoxib, indometacin, aspirin 순서로 혈관 반응성을 증가시켜, cyclooxygenase를 억제하면 혈관 수축성물질에 대한 반응성이 커질 수 있음을 나타낸다. 이중 cyclooxygenase에 대해 비가역적으로 강한 억제를 나타내는 aspirin이 제일 강한 효과를 나타내어 여기에 대한 연구는 더 필요할 것으로 생각된다. 혈관평활근 세포의 COX-2 단백질 발현은 indomethacin과 SNP, NOR-3 처치에 의해 증가되었으며, LPS를 이용하여 혈관염증을 유발 시키는 경우 혈관평활근 세포의 COX-2 단백질 발현이 증가되었고, 이 상태에서 SNP $100{\mu}M$ 전처치로 COX-2 단백질 발현을 감소되었으며, NOR-3 $100{\mu}M$은 COX-2 단백질 발현을 증가시켰다. LPS 유도 nitrite 생성에서 NOR-3는 SNP 보다 더 많은 nitrite를 생성시켰다. 이는 혈관의 수축반응에서 aspirin은 강한 상승작용을 유발하고, 혈관평활근 세포의 COX-2 발현은 NO 공여제, 혈관염증 유무에 따라 차이가 있는 것을 나타낸다.

• The Korean Journal of Physiology and Pharmacology
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• 제3권6호
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• pp.587-595
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• 1999

This study was designed to investigate effects of calcium antagonists on endothelial and neuronal dysfunction of right coronary artery (RCA) induced by ischemia- reperfusion in anesthetized, open-chest pigs. After reperfusion, pigs were sacrificed and the RCA was rapidly dissected for in vitro experiments. Experimental groups were divided into 4 groups: control (C-RCA), ischemia-reperfusion only (I-RCA), verapamil infusion (VI-RCA) and nifedipine infusion (NI-RCA) group, respectively. The ischemia did not affect hemodynamics, mean arterial pressure, heart rate, LVdP/dtmax, and decreased RCA flow. Arterial pressure and heart rate during ischemia-reperfusion were decreased in VI-RCA and NI-RCA, and RCA flow during reperfusion was increased in NI-RCA. 5-Hydroxytryptamine (5-HT) produced concentration-dependent contractions in C-RCA. The 5-HT-induced contractions were potentiated in I-RCA and VI-RCA, but not in NI-RCA. Endothelium-dependent relaxation by calcium ionophore A23187 was inhibited in I-RCA and VI-RCA, and recovered in NI-RCA. Cyclic GMP contents were decreased in I-RCA group alone. Electrical field stimulation in C-RCA produced transient and frequency-dependent contractions and at 50 Hz caused biphasic contractions. The transient contractions were not affected by pretreatment with phentolamine and atropine, but the biphasic contraction was altered by the pretreatment. Both contractions were inhibited in I-RCA, and were partially recovered in VI-RCA and NI-RCA. Ischemia-reperfusion of RCA in pigs causes endothelial and neuronal dysfunctions, and calcium antagonists partially prevent both.