• The Korean Journal of Physiology and Pharmacology
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• 제4권6호
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• pp.471-477
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• 2000

In the rabbit renal artery, acetylcholine $(ACh,\;1\;nM{\sim}10\;{\mu}M)$ induced endothelium-dependent relaxation of arterial rings precontracted with norepinephrine $(NE,\;1\;{\mu}M)$ in a dose-dependent manner. $N^G-nitro- L-arginine$ (L-NAME, 0.1 mM), an inhibitor of NO synthase, or ODQ $(1\;{\mu}M),$ a soluble guanylate cyclase inhibitor, partially inhibited the ACh-induced endothelium-dependent relaxation. The ACh-induced relaxation was abolished in the presence of 25 mM KCl and L-NAME. The cytochrome P450 inhibitors, 7- ethoxyresorufin $(7-ER,\;10\;{\mu}M),$ miconazole $(10\;{\mu}M),$ or 17-octadecynoic acid $(17-ODYA,\;10\;{\mu}M),$ failed to inhibit the ACh-induced relaxation in the presence of L-NAME. 11,12-epoxyeicosatrienoic acid $(11,12-EET,\;10\;{\mu}M)$ had no relaxant effect. The ACh-induced relaxation observed in the presence of L-NAME was significantly reduced by a combination of iberiotoxin $(0.3\;{\mu}M)$ and apamin $(1\;{\mu}M),$ and almost completely blocked by 4-aminopyridine (5 mM). The ACh-induced relaxation was antagonized by $P_{2Y}$ receptor antagonist, cibacron blue $(10\;and\;100\;{\mu}M),$ in a dose-dependent manner. Furthermore, 2-methylthio-ATP (2MeSATP), a potent $P_{2Y}$ agonist, induced the endothelium-dependent relaxation, and this relaxation was markedly reduced by either the combination of iberiotoxin and apamin or by cibacron blue. In conclusion, in renal arteries isolated from rabbit, ACh produced non-NO relaxation that is mediated by an EDHF. The results also suggest that ACh may activate the release of ATP from endothelial cells, which in turn activates $P_{2Y}$ receptor on the endothelial cells. Activation of endothelial $P_{2Y}$ receptors induces a release of EDHF resulting in a vasorelaxation via a mechanism that involves activation of both the voltage-gated $K^+$ channels and the $Ca^{2+}-activated\;K^+\;channels$. The results further suggest that EDHF does not appear to be a cytochrome P450 metabolite.

• 동의생리병리학회지
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• 제17권1호
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• pp.146-150
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• 2003

It had been known for a while that Crataegi Fructus(CF; Crataegus pinnatifida Bunge) had only a digestive effect. Recently, it has been demonstrated that CF also has an anti-hypertensive effect. However, its mechanism of relaxant effect has not been investigated yet. This study was examined to investigate the mechanism of vascular relaxation effect of CF in isolated rat thoracic aorta. CF revealed significant relaxation to phenylephrine(PE)-induced arterial contraction but much less to KCI-induced one. When CF was pretreated, it inhibited PE-induced contraction non-competitively. Methylene blue(10/sup -6/M) completely blocked the relaxant effect of CF whereas L-NAME(10/sup -5/M) did almost completely. However, atropine(10/sup -6/M) did not have any influence on vascular relaxation effect of CF. Regarding cNOS activity, CF significantly increased its activity from rat whole brain homogenate in a dose dependent manner which was inhibited by L-NAME(10/sup -5/M). On the other hand, CF did not affect on expression of TNF-α mRNA in RAW 264.7 cells, suggesting that CF is not related to iNOS activity. These results indicate that CF would be effective in relaxing vascular contraction through release of endothelial nitric oxide.

• The Korean Journal of Physiology
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• 제28권2호
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• pp.159-167
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• 1994

The contraction of rabbit basilar artery was examined as a function of changes in the $Na^+$ electrochemical gradient in order to determine the contribution of $Na^+/Ca^{2+}$ exchange to the modulation of contractility. Ouabain $(10^{-5}\;M)$ or $K^+-free$ Tyrode solution caused an increase in tonic tension even in the presence of a $Ca^{2+}$ channel blocker $(10^{-6}\;M\;verapamil)$ and an ${\alpha}-receptor$ blocker $(10^{-5}\;M\;phentolamine)$. After treatment with ouabain $(10^{-5}\;M)$, contractions were augmented by reduction of external $Na^+$ concentration. The longer the treatment with ouabain $(10^{-5}\;M)$ was, the larger the amplitude of $Na^+-free$ contracture was. $Na^+-free$ contracture wag induced by either substitution of equimolar Tris for $Na^+$ or substitution of equimolar $Li^+\;for\;Na^+$. The competition between $Na^+\;and\;Ca^{2+}$ for the $Na^+/Ca^{2+}$ exchange carrier would exist, because it was observed that contractility was dependent on the $Na^+$ electrochemical gradient or the extracellular $Ca^{2+}$ concentration (2 mM, 4 mM). Ryanodine $(10^{-7}\;M)$, the blocker of intracellular $Ca^{2+}$ release from the sarcoplasmic reticulum, did not suppress the development of $Na^+-free$ contracture. The contractile response to norepinephrine $(10^{-6}\;M)$ was augmented by reducing the extracellular $Na^+$ concentration. The relaxation rate from caffeine-induced contraction was dependent on the extracellular $Na^+$ concentration (0 mM, 140 mM). From the above results, it could be suggested that $Na^+/Ca^{2+}$ exchange can move $Ca^{2+}$ either into or out of rabbit basilar arterial smooth muscle. $Ca^{2+}$ entry or extrusion is dependent upon the $Na^+$ electrochemical gradient. $Na^+/Ca^{2+}$ exchange plays a significant role in the regulation of contractility in rabbit basilar arterial smooth muscle.

• Experimental and Molecular Medicine
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• 제50권12호
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• pp.11.1-11.9
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• 2018

Estrogen has diverse effects on cardiovascular function, including regulation of the contractile response to vasoactive substances such as serotonin. The serotonin system recently emerged as an important player in the regulation of vascular tone in humans. However, hyperreactivity to serotonin appears to be a critical factor for the pathophysiology of hypertension. In this study, we examined the modulatory mechanisms of estrogen in serotonin-induced vasoconstriction by using a combinatory approach of isometric tension measurements, molecular biology, and patch-clamp techniques. $17{\beta}$-Estradiol (E2) elicited a significant and concentration-dependent relaxation of serotonin-induced contraction in deendothelialized aortic strips isolated from male rats. E2 triggered a relaxation of serotonin-induced contraction even in the presence of tamoxifen, an estrogen receptor antagonist, suggesting that E2-induced changes are not mediated by estrogen receptor. Patch-clamp studies in rat arterial myocytes showed that E2 prevented Kv channel inhibition induced by serotonin. Serotonin increased Src activation in arterial smooth muscle required for contraction, which was significantly inhibited by E2. The estrogen receptor-independent inhibition of Src by E2 was confirmed in HEK293T cells that do not express estrogen receptor. Taken together, these results suggest that estrogen exerts vasodilatory effects on serotonin-precontracted arteries via Src, implying a critical role for estrogen in the prevention of vascular hyperreactivity to serotonin.

• Journal of Chest Surgery
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• 제31권9호
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• pp.884-892
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• 1998

우측 위대망동맥이 관상동맥 우회로 이식술에 사용되는 이식혈관으로서 관심을 끌게 된 것은 1980년대 중반 관동맥 우회로 이식술후 내유동맥의 장기 개통성이 복재정맥에 비하여 우수하다는 것이 알려진 다음부터였다. 처음에는 재수술을 하는 경우 등에서 사용 가능한 다른 이식혈관이 없을 때만 선택되었고 이식장소도 심장 후면에 위치하고 있는 후하행지 등에 제한되었으나, 최근에는 좌전하행지에도 이식되고 있고 위대망동맥의 중단기 개통성이 내유동맥의 것과 비슷한 것으로 보고된바 있으며, 일차 수술에서도 선택되는 경우가 늘어 나서 내유동맥과 복재정맥 다음으로 중요한 이식혈관이 되었다. 아직 장기 개통성이 알려 있지 않은 위대 망동맥에 대하여 이식도관으로서의 기능과 개통성 등을 연구하기 위해서 이 혈관의 수축성 및 이완성이 조사된 바 있으나 결과들이 일치하지 않고 있다. 본 실험에서는 위절제술을 받는 환자들에서 수술 중에 위대망동맥을 채취하여 고리절편으로 만든 후 organ bath내에 장치하여 혈관 수축제 및 이완제에 대한 반응을 측정함으로써 도관으로서의 가치 평가를 함과 동시에 이식된 도관의 경련발생 및 이의 치료를 위한 이완제 투여 등에 관해 연구하였다. 수축제들 중 epinephrine, noprepinephrine 및 KCl은 강한 수축력을 보였고 5-HT의 수축력이 가장 약했으며 전자들의 것과 비교했을 때 유의한 차이를 보였다. Nitroprusside과 histamine은 norepinephrine으로 유도된 수축의 거의 전부를 이완시켰으며 acetylcholine의 이완력은 이들의 것에 비해 유의하게 약했다. 이완제들중 isoproterenol의 이완력이 가장 약했으며 나머지 이완제들의 것과 비교했을 때 유의한 차이를 보였다. 이상에서 위대망동맥의 강한 내피세포 의존성 이완력은 본 혈관이 관상동맥우회로이식술에 도관으로 사용되었 을 때 개통성 유지에 중요한 역할을 할 것이고, 위대망동맥은 catecholamine에 대한 반응이 커서 관상동맥우회 로이식술후 혈중 catecholamine치료가 상승하는 경우에는 이식된 위대망동맥에 경련이 발생할 가능성이 있으며, 이의 치료에는 nitroprusside가 효과적일 것으로 추정된다. 또한 내피세포가 보존된 위대망동맥의 beta-adrenoceptor 촉진제 및 5-HT에 대한 반응은 약할 것으로 생각된다.

• The Korean Journal of Physiology and Pharmacology
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• 제8권6호
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• pp.313-317
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• 2004

The present study were designed to characterize the action mechanisms of acetylcholine (ACh)-induced endothelium-dependent relaxation in arteries precontracted with high $K^+$(70 mM). For this, we simultaneously measured both muscle tension and cytosolic free $Ca^{2+}$ concentration $([Ca^{2+}]_i)$, using fura-2, in endothelium-intact, rabbit carotid arterial strips. In the artery with endothelium, high $K^+$ increased both $[Ca^{2+}]_i$ and muscle tension whereas ACh $(10{\mu}M)$ significantly relaxed the muscle and increased $[Ca^{2+}]_i$. In the presence of $N^G$-nitro-L-arginine (L-NAME, 0.1 mM), ACh increased $[Ca^{2+}]_i$ without relaxing the muscle. In the artery without endothelium, high $K^+$ increased both $[Ca^{2+}]_i$ and muscle tension although ACh was ineffective. 4-DAMP (10 nM) or atropine $(0.1{\mu}M)$ abolished ACh-induced increase in $[Ca^{2+}]_i$ and relaxation. The increase of $[Ca^{2+}]_i$ and vasorelaxation by ACh was siginificantly reduced by either $3{\mu}M$ gadolinium, $10{\mu}M$ lanthanum, or by $10{\mu}M$ SKF 96365. These results suggest that in rabbit carotid artery, ACh-evoked relaxation of 70 mM $K^+$-induced contractions appears to be mediated by the release of NO. ACh-evoked vasorelaxation is mediated via the $M_3$ subtype, and activation of the $M_3$ subtype is suggested to stimulate nonselective cation channels, leading to increase of $[Ca^{2+}]_i$ in endothelial cells.

• 동의생리병리학회지
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• 제22권1호
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• pp.131-136
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• 2008

This study was undertaken to define the effect of Polygoni cuspidatae Radix on contracted rabbit common carotid artery and its mechanism. In order to investigate the effect of Polygoni cuspidatae 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 cuspidatae Radix-induced relaxation, Polygoni cuspidatae 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 or KCl after treatment of Polygoni cuspidatae Radix extract in $Ca^{2+}-free$ solution. The results were as follows : Polygini cuspidatae Radix had an effective relaxation to the contracted vascular ring by NE in 0.1 mg/ml and 0.3 mg/ml level. Polygini cuspidatae Radix had an effective relaxation to the intact endothelium vascular ring, but when endothelium was removed, vascular ring did not relax. Polygini cuspidatae Radix-induced relaxation was inhibited by the pretreatment of L-NNA and MB. Pretreatment of Polygini cuspidatae Radix extract inhibit the contraction by influx of $extra-Ca^{2+}$ in contracted vascular ring induced by NE or KCl in $Ca^{2+}-free$ solution. As mentioned above, we suggest that Polygini cuspidatae Radix relaxes vascular ring through suppress influx of extra-cellular $Ca^{2+}$ by the action of nitric oxide from endothelium.

• 대한수의학회지
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• 제42권3호
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• pp.321-326
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• 2002

The effect of nitric oxide synthase(NOS) inhibita, $N^G$-nitro-L-arginine-methyl ester(L-NAME) and prostanoid synthesis inhibiter, indomethacin on the photorelaxation, when was exposed to the long-wave length UV-light, was examined on the precontraction by the phenylephrine in the isolated pig renal artery. 1. UV-light relaxed both with-endothelium and without-endothelium in the pig renal arterial ring contracted by the phenylephrine. The magnitude of photorelaxation was dependent on the exposure time for UV-light. 2. UV-Iight induced relaxation was inhibited by L-NAME and indomethacin on the precontraction by the phenylephrine in the isolated pig renal artery. 3. UV-Iight induced relaxation was inhibited by methylene blue on the precontraction by the phenylephrine in the isolated pig renal artery. These results suggest that UV-light induced photorelaxation may be due to cGMP involved both nitric oxide and prostanoid on the precontraction by the phenylephrine in the isolated pig renal artery.

• 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.

• 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.