• 대한수의학회지
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• 제43권4호
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• pp.597-606
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• 2003

Although the antidepressant effects of imipramine (IMI) have been well known in several studies, the effects on cardiovascular system, particularly the vasorelaxant effects, have not known clearly. We hypothesis that IMI-induced vasorelaxation involves NO (nitrie oxide), activation of guanylate cyclase (GC) and $Ca^{2+}$ channel. The possible roles of the endothelium and $Ca^{2+}$ in IMI-induced responses were investigated using isolated rings of rat thoracic aorta and anesthesized rats. In KCl-precontracted rings. IMI produces endothelium-dependent and endothelium-independent relaxations in intact (+E) as well as endothelium-denuded (-E) rat aorta in a concentration-dependent manner. In phenylephrine (PE)-precontracted rings, the IMI-induced relaxation was significantly greater in +E rings. The IMI-induced relaxations were suppressed by nitric oxide synthase (NOS) inhibitors, N(G)-nitro-L-arginine (L-NNA), N(omega)-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine, a non-selective GC inhibitor, methylene blue, $Na^+$ channel blockers, lidocaine and procaine, or $Ca^{2+}$ channel blockers, nifedipine and verapamil, in PE-precontracted +E rings, but not in PE-precontracted -E rings. These relaxations were also suppressed by lidocaine or procaine in -E aortic rings. However, IMI-induced relaxations were not inhibited by a PLC inhibitor 2-nitro-4-carboxyphenyl-n,n-diphenylcarbamate (NCDC), an inositol monophosphatase inhibitor, lithium, indomethacin and dexamethasone in +E and -E rings. In vivo, infusion of IMI elicited significant decrease in arterial blood pressure. After intravenous injection of saponin, NOS inhibitors. MB and nifedipine, infusion of IMI inhibited the IMI-lowered blood pressure markedly. These findings suggest that the endothelium-dependent relaxation induced by IMI is mediated by activation of NO/cGMP signaling cascade or inhibition of $Ca^{2+}$ entry through voltage-gated channel, and this mechanism may contribute to the hypotensive effects of IMI in rats.

• The Korean Journal of Physiology and Pharmacology
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• 제2권6호
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• pp.695-703
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• 1998

$[K^+]_o$ can be increased under a variety of conditions including subarachnoid hemorrhage. The increase of $[K^+]_o$ in the range of $5{\sim}15$ mM may affect tensions of blood vessels and can change their sensitivity to various vasoactive substances. Therefore, it was examined in the present study whether the sensitivity of cerebral arteries to vasoactive substances can be changed with the moderate increase of $[K^+]_o$, using Mulvany-type myograph and $[Ca^{2+}]_c$ measurement. The contractions of basilar artery and branch of middle cerebral artery induced by histamine were not increased with the elevation of $[K^+]_o$ from 6 mM to 9 mM or 12 mM. On the contrary, the contractions induced by serotonin were significantly increased with the elevation of $[K^+]_o$. The contractions were also significantly increased by the treatment with nitro-L-arginine $(10^{-4}$ M for 20 minutes). In the nitro-L-arginine treated arteries, the contractions induced by serotonin were significantly increased with the elevation of $[K^+]_o$ from 6 mM to 12 mM. $K^+-induced$ relaxation was evoked with the stepwise increment of extracellular $K^+$ from 0 or 2 mM to 12 mM by 2 mM in basilar arterial rings, which were contracted by histamine. But $[K^+]_o$ elevation from 4 or 6 mM to 12 mM by the stepwise increment evoked no significant relaxation. Basal tension of basilar artery was increased with $[K^+]_o$ elevation from 6 mM to 12 mM by 2 mM steps or by the treatment with ouabain and the increase of basal tension was blocked by verapamil. The cytosolic free $Ca^{2+}$ level was not increased by the single treatment with serotonin or with the elevation of $[K^+]_o$ from 4 mM to 8 or 12 mM. In contrast to the single treatment, the $Ca^{2+}$ level was increased by the combined treatment with serotonin and the elevation of $[K^+]_o$. The increase of free $Ca^{2+}$ concentration was blocked by the treatment with verapamil. These data suggest that the sensitivity of cerebral artery to serotonin is increased with the moderate increase of $[K^+]_o$ and the increased sensitivity to serotonin is due to the increased $[Ca^{2+}]_i$ induced by extracellular $Ca^{2+}$ influx.

• 한국환경과학회지
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• 제12권6호
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• pp.651-657
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• 2003

In order to examine if arsenic, one of environmental stresses, contributes to hypertension as one of cardiovas cular pathological factors, this study was perfarmed in vivo and in vitro, using intacted or pithed rats and aorta ring preparation, respectively. And also the relationship between expression of heat shock protein (HSP) 90 and vasoactives-induced contractile response was elucidated. To measure blood pressure, the carotid arterial pressure was recorded on physiograph(Grass Co. 79E) connected to strain gauge. On the other hand, contractile response of vascular ring preparation isolated from rat was determined in organ bath and was recorded on physiograph connected to isometric transducer. And HSP was detacted by Western blotting whole cell Iysis. Preganglionic nerve stimulation was increased by 26.0% in arterial pressure of rat treated with arsenic. Vascular contractile response was monitored and HSP were measured by Western blotting of whole Iysis prepared from samples exposed with 0, 0.5, 1, 2 and 4 mM of arsenic for 8 hours. The dose-vascular responses of potassium chloride were augmented by increasing dose of arsenic in the strips exposed to arsenic for 8 hours, and were not augmented for 1, 3, 5 hours. And the response of relaxation of rat aorta induced by histamine was not influenced by arsenic stress. The increase of HSP 90 expression in rat aorta was pronounced at 8 hours after 4 mM of arsenic treatment, but HSP 60 expression was not. Arsenic stress not only increased the expression of HSP 90 in the rat aorta, but also augmented contractions to potassium chloride. These results indicated that arsenic stress was sufficient to induce heat shock protein 90, resulting in increased vascular contractility in rat aorta.

• 한국방사선학회논문지
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• 제9권4호
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• pp.213-217
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• 2015

스텐트 삽입술을 시행한 환자에게 ASL 방법 중 pCASL을 이용한 관류영상에서 나타난 인공물을 보고하고 이에 대한 해결방법을 제시하고자 한다. pCASL데이터는 구조적 이미지와 함께 스텐트를 피해 표지 펄스(labeling pulse)의 위치를 변경하여 획득하였다. 데이터는 ASLtbx를 이용하여 처리하였다. pCASL을 이용하여 관류영상을 획득하였을 때 기존의 표지 펄스(표지 간격(labeling gap) 24 mm)의 위치가 스텐트의 위치와 겹쳐져서 우뇌 조직의 신호강도가 비어 있는 것처럼 나타났다. 스텐트를 피해 표지 펄스(표지 간격 15 mm)를 위치시킬 때 높은 신호강도의 영상을 획득할 수 있었으며, 표지 펄스(표지 간격 170 mm)에서는 labeled 혈액이 영상절편에 도달하기 전에 이완이 되어 낮은 신호강도의 영상을 획득 하였다. pCASL은 조영제를 사용하지 않기 때문에 안정적으로 반복측정이 가능하며 양질의 영상 획득을 위해서는 알맞은 영상획득인자와 방법들이 선택되어야 한다.

• The Korean Journal of Physiology and Pharmacology
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• 제5권5호
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• pp.413-421
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• 2001

An impaired smooth muscle cell (SMC) relaxation of coronary artery by alteration of $K^+$ channels would be the most potential explanation for reduced coronary reserve in left ventricular hypertrophy (LVH), however, this possibility has not been investigated. We performed morphometrical analysis of the coronary artery under electron microscopy and measured $Ca^{2+}-activated\;K\;(K_{Ca})$ currents and delayed rectifier K $(K_{dr})$ currents by whole-cell and inside-out patch-clamp technique in single coronary arterial SMCs from rabbits subjected to isoprenaline-induced cardiac hypertrophy. Coronary arterial SMCs underwent significant changes in ultrastructure. The unitary current amplitude and the open-state probability of $K_{Ca}$ channel were significantly reduced in hypertrophy without open-time and closed-time kinetic. The concentration-response curve of $K_{Ca}$ channel to $Ca^{2+}$ is shifted to the right in hypertrophy. The reduction in the mean single channel current and increase in the open channel noise of $K_{Ca}$ channel by TEA were more sensitive in hypertrophy. $K_{dr}$ current density is significantly reduced in hypertrophy without activation and inactivation kinetics. The sensitivity of $K_{dr}$ current on 4-AP is significantly increased in hypertrophy. This is the first study to report evidence for alterations of $K_{Ca}$ channels and $K_{dr}$ channels in coronary SMCs with LVH. The findings may provide some insight into mechanism of the reduced coronary reserve in LVH.

• 대한수의학회지
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• 제44권3호
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• pp.389-397
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• 2004

The therapeutic efficacy of xylamine in the field of psychological medicine has been recognized for years and the drug is used to treat depression and some other conditions, but little is known about its mechanism of action on vascular system. Therefore, the present study was designed to investigate the influence of xylamine on the contractile responses of isolated rat thoracic arteries to phenylephrine(PE) and potassium chloride(KCl). Xylamine produced a concentration-dependent relaxation in PE-precontracted endothelium intact(+E) rat aortic rings, but not in a KCl-precontracted aortic rings. Also, xylamine inhibited the PE-induced contraction in concentration-dependent manner, but not in the high KCl-induced contraction in +E rings. This concentration-dependent inhibition was suppressed by the removal of the endothelium (-E). The inhibitory effects of xylamine($0.3{\mu}M$) on the PE-induced contractions were suppressed by N(G)-nitro-L-arginine(L-NNA), N(omega)-nitro-L-arginine methyl ester(L-NAME), aminoguanidine, dexamethasone, methylene blue, 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one(ODQ), indomethacin, ryanodine, tetrabutylammonium(TBA), lidocaine, procaine and 0 mM extracellular $Na^+$, but not by 2-nitro-4-carboxyphenyl-n,n-diphenylcarbamate(NCDC), lithium, nifedipine, verapamil, 0 mM extracellular $Ca^{2+}$, glibenclamide and clotrimazole. These findings suggest that xylamine could act as a vasorelaxant and direct inhibitor of arterial contraction. This vasorelaxation involves an endothelial nitric oxide (NO)/cGMP (guanosine 3',5'-cyclic monophosphate) pathway or cyclooxygenase system, and an interference with $Ca^{2+}$ release, TBA-sensitive $Ca^{2+}$-activated $K^+$ channels and $Na^+$$ channels.

• 대한수의학회지
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• 제43권4호
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• pp.587-595
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• 2003

The aim of this study was to investigate trazodone's effect on vasorelaxation and blood pressure lowering and to examine its underlying mechanism of action in isolated thoracic aorta and anesthesized rats. Precontracted aortic rings with high KCl were relaxed with trazodone, at concentrations of $50{\mu}M$ or greater. However, precontracted rings with phenylephrine (PE) were relaxed with trazodone, at concentrations of $0.03{\mu}M$ or greater, in a concentration-dependent manner. These relaxant effects of trazodone on endothelium intact rat aortic rings were significantly greater than those on denuded rings. The trazodone-induced relaxations were suppressed by nitric oxide synthase (NOS) inhibitors, N(G)-nitro-L-arginine (L-NNA) and N(omega)-nitro-L-arginine methyl ester (L-NAME), guanylate cyclase inhibitors, methylene blue and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a $Ca^{2+}$-activated $K^+$ channel blocker, tetrabutylammonium (TBA), a $Ca^{2+}$ channel blocker, nifedipine, $Na^+$ channel blockers, lidocaine and procaine, and removal of extracellular $Na^+$, but not by aminoguanidine, 2-nitro-4-carboxyphenyl-n, n-diphenylcarbamate (NCDC), indomethacin, glibenclamide and clotrimazole. In vivo, infusion of trazodone elicited significant decrease in arterial blood pressure. Trazodone-induced decrease in blood pressure was markedly inhibited by pretreatment of intravenous injection of saponin, L-NNA, methylene blue, TBA, lidocaine or nifedipine. These findings suggest that the endothelium-dependent relaxation and decrease in blood pressure induced by trazodone is mediated by release of NO from the endothelium, activation of TBA-sensitive $Ca^{2+}$-activated $K^+$ channels or inhibition of $Ca^{2+}$ entry through voltage-gated channel.

• The Korean Journal of Physiology and Pharmacology
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• 제1권4호
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• pp.393-402
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• 1997

In the present study, we characterized the angiotensin II (AII)-induced relaxations in the phenylephrine-precontracted rabbit mesenteric arteries with endothelium. 1) AII-induced relaxation was consistently observed in the rabbit mesenteric arteries with and without endothelium, but not in the aortic segment with endothelium. 2) AII-induced endothelium-dependent relaxation was markedly inhibited by $N^w-nitro-L-arginine$ (L-NNA, $100\;{\mu}M$), methylene blue ($10\;{\mu}M$) and LY83583 ($10\;{\mu}M$), respectively. 3) Inhibition of cyclooxygenase with indomethacin ($10\;{\mu}M$) strongly decreased the vasorelaxant response to AII irrespective of the presence of endothelium. 4) 7-Ethoxyresorufin ($1\;{\mu}M$) and clotrimazole ($1\;{\mu}M$), inhibitors of cytochrome P-450-dependent arachidonic acid metabolism, greatly attenuated the vasodilator response to AII. 5) Carbacyclin, arachidonic acid and prostaglandin $F_{2{\alpha}}$ ($PGF_{2{\alpha}}$) caused concentration-dependent relaxations in the mesenteric artery with endothelium, which were inhibited by L-NNA and methylene blue. 6) AII and $PGF_{2{\alpha}}$ significantly stimulated cyclic GMP formation in the mesenteric arteries with endothelium, which was inhibited by L-NNA and methylene blue, respectively. 7) AII enhanced synthesis of $PGF_{2{\alpha}}$ and 6-keto $PGF_{1{\alpha}}$ from the arterial segments with endothelium, which was inhibitable by indomethacin, but not by L-NNA. In conclusion, the vasorelaxant responses to AII of the rabbit mesenteric artery with endothelium are subserved by arachidonic acid and its metabolites produced via activation of cyclooxygenase and cytochrome P-450 enzyme as well as by nitric oxide.

• Journal of Chest Surgery
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• 제28권12호
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• pp.1079-1095
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• 1995

Recently endogenous digitalis-like substances were found in the blood of various cardiovascular diseases and they have been considered one of the causes of evoking hypertension. However, the mechanism of endogenous digitalis-like substances-induced hypertension is not clarified yet. Therefore, the effects of Na-K pump inhibition on the contractility of vascular smooth muscle[conduit and resistant artery were investigated, using organ bath and bioassay experiment. Aortic and carotid arterial rings[conduit artery and the branches of brachial and superior mesenteric artery[resistant artery were used to find the effect of Na-K pump inhibition. The results obtained were as followes;The magnitudes of contractions induced by norepinephrine, serotonin, or acetylcholine in all these arteries were significantly increased by the inhibition of Na-K pump. The increased contractile responses to these agonists, especially to serotonin, were much more prominant in resistant arteries. Nitroprusside-induced relaxations were attenuated by Na-K pump inhibition and there were no significant differences in the effects of Na-K pump inhibition on nitroprusside-induced relaxations of these blood vessels. Endothelium-dependent relaxation was suppressed by the inhibition of Na-K pump, especially by the administration of ouabain, and this inhibitory effect was much more prominent in the branches of superior mesenteric artery, compared with other arteries. In the branches of superior mesenteric arteries, endothelium-dependent relaxation was completely blocked by ouabain. The release of EDRF was partially suppressed by Na-K pump inhibition.From the above results, it is suggested that the hypertension due to the increase in vascular resistance can be evoked by the inhibition of Na-K pump and endogenous digitalis-like substances induce hypertension through this mechanism.

• 여성건강간호학회지
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• 제7권2호
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• pp.188-202
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• 2001

This study was designed to investigate the effect of one-to-one labor support on labor pain, labor stress response, childbirth experience and neonatal status for primipara by a quasi experiment (nonequivalent control group pretest-posttest design), from April 30, 1999 to February 20, 2000. The subjects of this experiment consisted of eighty two primipara with single gestation, full term, uncomplicated pregnancies. Forty one were in the experimental group and forty one in the control group. Their mean age was 25.95 years, their mean gestation period was 39.9 weeks. A caring package of one-to-one labor support had three components. Physical support consisted of massage, back pressure, touch. Emotional support was provided by a continuous nurse's presence, acceptance and encouragement. Informational support involved teaching breathing skills, relaxation skills and knowledge about the labor process. Data assessed labor pain, pulse rate and blood pressure to measure labor stress response. Also, in measuring the value of labor stress response, plasma epinephrine, plasma norepinephrine and serum cortisol were measured. In the 24 hours after birth, the data for the postpartum mother's childbirth experiences was collected. Umbilical cord arterial blood pH, one minute and five minute Apgar score were measured after birth. Data was analyzed by t-test, $x^2$-test, repeated measures ANOVA, ANCOVA with SAS Program. The results were as follows; 1. Labor pain was significantly low in the experimental group(P=.016). 2. No significant group effects were found, but significant time effects were found for plasma epinephrine, norepinephrine, serum cortisol, pulse rate and blood pressure. 3. The childbirth experience of the experimental group was significantly more positive than the control group (P = .005). 4. The umbilical cord arterial blood pH of the experimental group was significantly higher than the control group(P=.014). There was no significant difference between the two groups in neonatal one minute and five minute Apgar scores. In conclusion, these findings indicate that one-to-one labor support could be effective in decreasing labor pain, and increasing positive childbirth experiences, also increasing the neonatal umbilical cord arterial blood pH for primipara. So, one-to-one labor support could be applied as an effective nursing treatment for primipara.