• The Korean Journal of Physiology
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• v.30 no.2
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• pp.269-278
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• 1996

The mechanism of impaired endothelium-dependent relaxation in the aorta of one-kidney, one clip Goldblatt hypertensive (1K,1C-GBH) rats was investigated. 8 week-old Wistar-Kyoto (WKY) rats were made hypertensive by left renal artery stenosis with contralateral nephrectomy. Endothelium-dependent relaxation was significantly reduced in 1K,1C-GBH rats as compared with WKY rats. However, the relaxation by sodium nitroprusside in 1K,1C-GBH rats was not reduced as compared with WKY rats. The impairment of endothelium-dependent relaxation in 1K,1C-GBH rats was partially restored by the pretreatment of indomethacin or SQ29548. When the nitric oxide production was inhibited by L-nitroarginine methyl ester, acetylcholine (ACh) induced a endothelium-dependent contraction that was greater in 1K,1C-GBH rats than in WKY rats. Endothelium-dependent contraction by ACh was completely abolished by indomethacin or SQ29548. However, imidazole, tranylcypromine and superoxide dismutase did not affect the endothelium-dependent contraction in 1K,1C-GBH rats. These results suggest that impaired endothelium-dependent relaxation in the 1K,1C-GBH rats might be due to the simultaneous release of EDCF, and that prostaglandin B2 may be involved as a mediator of endothelium-dependent contraction.

• The Korean Journal of Physiology
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• v.30 no.1
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• pp.21-31
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• 1996

To investigate the mechanisms of increased endothelium-dependent contraction by acetylcholine in hypertensive rats, the relationship between endothelium-dependent contraction by acetylcholine and blood pressure was studied in spontaneously hypertensive rats (SHR), one-kidney, one clip Goldblatt hypertension (1K,1C-GBH) rats, and Wistar-Kyoto rats (WKY). SHR were treated orally with enalapril or nicardipine in order to prevent development of hypertension or suppress the developed hypertension. 1K,1C-GBH rats were made by renal artery stenosis with contralateral nephrectomy in 8 week-WKY. 1. Endothelium-dependent contractions by acetylcholine $(10^{-6}{\sim}10^{-5}\;M)$ in SHR were significantly greater than those in WKY. 2. Chronic treatment with enalapril or nicardipine reduced the endothelium-dependent contraction in SHR 3. The degree of reduction of endothelium-dependent contraction was greater in SHR which was prevented from developing hypertension than in SHR of which high blood pressure was suppressed. 4. In aortic rings from 1K,1C-GBH rats, endothelium-dependent contractions by acetylcholine were augmented as compared with WKY. 5. There is good relationship between the value of blood pressure and magnitude of endothelium-dependent contraction. Thus, it is suggested that increased endothelium-dependent contraction in hypertensive rats may he due to the high blood pressure and endothelium-dependent contraction may not be a cause of the initiation of hypertension in SHR.

• YAKHAK HOEJI
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• v.34 no.3
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• pp.180-191
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• 1990

A comparison was made of the effects of selective ${\alpha_1}-adrenoceptor$ agonist phenylephrine and selective ${\alpha_2}-adrenoceptor$ agonist clonidine on endothelium-containing and endothelium-denuded rings of the rat aorta. In the case of phenylephrine, removal of endothelium increased sensitivity 2.5 fold at $EC_{50}$ level and maximum contractive response 1.4 fold. In the case of clonidine, which gave only 15% of maximum contractive response given to phenylephrine on endothelium-containing rings, removal of the endothelium increased sensitivity 5.6 fold at $EC_{50}$ level and maximum contractive response 5 fold, which was about 55% of that given by phenylephrine. In endothelium-denuded ring, phenylephrine-induced contraction tended to be more increased in tonic contraction than in phasic contraction as compared to that in endothelium-containing ring, while clonidine-induced contraction was monophasic and was increased only in tonic contraction. In the calcium-free solution or in the presence, of verapamil, contraction stimulated by clonidine was almost abolished while that stimulated by phenylephrine produced only phasic contraction. The depression of sensitivity to these agonists in rings with endothelium appeared to be due to the vasodepressor action of endothelium derived relaxing factor (EDRF), because hemoglobin, a specific blocking agent of EDRF, abolished this depression. It is unlikely that the endothelium-dependent relaxation was due to stimulation of release of EDRF, because clonidine did not produce endothelium-dependent relaxation in 5-hydroxytryptamine-precontracted ring even when its contractile action was blocked by the ${\alpha_1}-adrenoceptor$ antagonist, prazosin. When the efficacy of phenylephrine was reduced to about the initial efficacy of clonidine by pretreatment with dibenamine, the contraction-response curves for phenylephrine became very similar to the corresponding curves obtained for clonidine before receptor inactivation. In the dibenamine-treated rings, contraction of phenylephrine was abolished in calcium-free solution or in the presence of verapamil like that obtained for clonidine before receptor inactivation. These results suggest that EDRF spontaneously released from endothelium depress contraction more profoundly in a case of an agonist with low efficacy and the phenylephrine-induced contraction was totally dependent on extracellular calcium as was that obtained for clonidine when the efficacy of phenylephrine was reduced to that of clonidine by irreversible inactivation of ${\alpha_1}-adrenoceptor$ with dibenamine.

• Journal of Ginseng Research
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• v.29 no.3
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• pp.119-125
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• 2005

The previous reports demonstrated that ginseng saponins, active ingredient of Panax ginseng, inhibited blood vessel contraction induced by various hormones or high $K^+$. Recently, we demonstrated that 20(R)- and 20(S)-ginsenoside $Rg_3$. regulate ion channel activities with differential manners. The aim of this study was to examine whether ginsenoside $Rg_3$ isomers also show differential effects on swine coronary artery contractionresponses induced by high $K^+$, serotonin (5-HT) or acetylcholine. Treatment of 20(S)- but not 20(R)-ginsenoside $Rg_3$ caused a concentration-dependent relaxation of coronary artery contracted by 25mM KCI. 20(S)- and 20(R)-ginsenoside $Rg_3$ induced significant relaxations of coronary artery contraction induced by 5-HT $(3{\mu}M)$ in the presence of endothelium with concentration-dependent manner and, also in the absence of endothelium only 20(S)-ginsenoside $Rg_3$ induced a strong Inhibition of coronary artery contraction induced by 5-HT in a concentration-dependent manner. 20(S)-ginsenoside $Rg_3$ caused relaxation of coronary artery in the absence and presence of endothelium. In contrast, treatment of 20(S)- and 20(R)-ginsenoside $Rg_3\;(100{\mu}M)$ did not show significant inhibition of coronary artery contraction induced by acetylcholine $(0.01\;to\;30{\mu}M)$ in the presence of endothelium, whereas both isomers caused significant inhibition of coronary artery contraction induced by acetylcholine $(0.01\;to\;30{\mu}M)$ in the absence of endothelium in a concentration-dependent manner. These findings indicate that 20(S)-or 20(R)-ginsenoside $Rg_3$ exhibits differential relaxation eff3cts of swine coronary artery contractions caused by high $K^+$, acetylcholine, and 5-HT treatment and that this differential vasorelaxing effects of ginsenoside $Rg_3$ isomers also might be dependent on endothelium.

• The Journal of Korean Medicine
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• v.24 no.4
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• pp.82-86
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• 2003

Objective : To examine the inhibition of 5-Hydroxytryptamine(5-HT) induced vasocontraction of the water extract of Acanthopanax senticosus Harms roots (ASR) on rat thoracic Aorta and mesenteric artery with and without endothelium. Methods : Segments of thoracic aorta and mesenteric artery obtained from rats immediately after delivery were mounted in organ baths superfused on a polygraph. Results : We found that the thoracic aorta segments responded to the water extract of ASR with a dose-dependent and concentration-dependent vasorelaxation. 5-HT produced a concentration-dependent contraction of the thoracic aorta and mesenteric artery. At high concentrations of ASR, the inhibition responses were 93.7% (Jang-su), 93.5% (Heok-ryong-kang-sung), 92.8% (Mt. Back-doo), and 83.5% (Yeon-byun) of the maximum 5-HT induced contraction. At high concentrations of ASR, the relaxational response at thoracic aorta and mesenteric artery wi1h endothelium were 95.2% and 94.6%; without endothelium were 93.5% and 92.5% of 1he maximum 5-HT induced contraction. Conclusions : In conclusion, the effect of water extract of ASR had potent inhibition at 5-HT and the effect of ASR in isolated thoracic aorta and mesenteric artery showed dose-dependent inhibition but endothelium-independent response.

• Korean Journal of Veterinary Research
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• v.34 no.4
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• pp.727-734
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• 1994

To elucidate the effect of calcitonin gene-related peptide(CGRP), vasoactive intestinal peptide(VIP) and substance P was investigated with perivascular nerve stimulation and treatment of peptides from polygraph in the isolated renal artery of rabbit. 1. The neurogenic contraction induced by perivascular nerve stimulation was the frequency-dependent manner(264 Hz) in the isolated renal artery of rabbit. 2. CGRP and VIP caused the relaxation on the precontraction with noradrenaline($10{\mu}m$) on the presence and absence of endothelium in the isolated renal artery of rabbit. 3. Substance P caused the endothelium-dependent relaxation on the precontraction with noradrenaline($10{\mu}m$) in the isolated renal artery of rabbit. 4. CGRP and VIP inhibited the neurogenic contraction by the perivascular nerve stimulation(0.3 ms, 80 V, 50 Hz, 1 sec) on the absence and presence of endothelium in the isolated renal artery of rabbit. 5. Substance P inhibited on the neurogenic contraction by the perivascular nerve stimulation with the endothelium-dependent in the isolated renal artery of rabbit.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.1
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• pp.67-71
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• 2002

This study investigated the relaxation effects of Crataegi Fructus(CF, Crataegus pinnatifida Bunge) on the contraction evoked by phenylephrine in rabbit carotid artery, and also analyzes antioxidative status in vitro. CF revealed siginificant relaxation on phenylephrine-induced arterial contraction. It's relaxant effect statistically significant in both in the presence of endothelium and absence of endothelium, but statistically exerted more strong relaxation in the presence of endothelium. CF increased in vitro nitric oxide(NO) production in dose-dependent manner. Also, they reduced malondiaidehyde(MDA) concentrations, phosphatidyl choline-liposome(PCOOH) contents, linoleic acid-induced lipid peroxidation and exerted 1,1-diphenyl-2- picryl-hydrazyl(DPPH) radical scavenging effect, in vitro. These results indicate that Crataegi Fructus would be effective in relaxing arterial contraction and it's antioxidative effects may be involved in endothelium-dependent relaxation of artery via vascular protective properites.

• The Journal of Korean Medicine
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• v.21 no.1
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• pp.77-83
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• 2000

This study investigated the effects of Siegesbeckia glabrescens, an antihypertensive remedy, on the contraction evoked by phenylephrine and KCl in isolated rat thoracic arata, and also analyzed antioxidative status in vitro. Siegesbeckia glabrescens revealed dose-dependent relaxation on phenylephrine(PE)/KCl-induced arterial contraction and more markedly on PE-induced contraction. Siegesbeckia glabrescens reduced malondialdehyde(MDA)levels, Phosphatidyl choline-liposome(PC-OOH) contents, linoleic acid-induced lipid peroxidation and exerted 1,1-diphenyl-2- picryl-hydrazyl(DPPH) radical scavenging effect, in vitro. These results indicated that Siegesbeckia glabrescens doesn't relaxe artery through a blocking α-adrenergic receptor and calcium channel mediated by voltage-operated calcium channel, and it s antioxidative effects may be involved in endothelium-dependent relaxation of arteries via vascular protective properites. (J Korean Oriental Med 2000;21(1):77-83)

• The Korean Journal of Pharmacology
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• v.24 no.2
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• pp.203-216
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• 1988

To delineate the mechanisms of vasoconstriction and vasodilation in cerebral arteries the effects of some vasoconstrictors and calcium antagonists on the basilar artery (BA) and arterial circle of Willis (WC) were examined and also the role of endothelium in the action of these drugs was investigated in pigs, cats and rabbits. In pig cerebral arteries, dose-dependent contractile responses were elicited by KCI, histamine, 5-hydroxytryptamine (5-HT) and angiotensin, but norepinephrine (NE), phenylephrine (PE) and epinephrine (EP) elicited dose-dependent contractions only under pretreatment with propranolol 10-6 M. The magnitudes of maximal contractile effects of these drugs were different from each other, and 5-H~ was the largest and angiotensin the smallest. Some calcium antagonists dose-dependently inhibited KCI (35 mM)-induced contraction and the order of potency in inhibiting the contraction was nifedipine > > diltiazem > flunarizine > oxybutynin > isosorbide dinitrate (ISDN) > glyceryl trinitrate. 5-HT (10-6 M)-induced contraction was dosedependently inhibited by nifedipine but slightly inhibited by diltiazem and ISDN. In rings with intact endothelium, KCI (35 mM)-induced contraction was not affected by acetylcholine (ACh) but $PGF_{2{\alpha}}$ (lO-SM)-induced contraction was dose-dependently relaxed by ACh and adenosine. This endothelium-dependent relaxation was not affected by nifedipine (l0-6M)-pretreatment but markedly inhibited by methylene blue (50,uM)-pretreatment. In the porcine arterial rings without endothelium, ACh had no effect or even contracted the $PGF_{2{\alpha}}-induced$ contraction. However, the dosedependent relaxing effect of ACh appeared when the deendothelized porcine ring and rabbit thoracic aorta with intact endotheli urn were simultaneously suspended into a bath and this relaxing effect was also inhibited by methylene blue-pretreatment. In cat cerebral arteries, 5-HT and NE elicited dose-dependent contractile responses and ACh also produced dose-dependent contraction regardless of the existence of endothelium. ACh-induced contraction was most prominent. 5-HT (IO-SM)induced contraction was not relaxed but contracted additionally by ACh even in the intact endothelial ring. In rabbit cerebral arteries, 5-HT and NE elicited dose-dependent contractile responses and 5-HT-induced contraction was more prominent. In the intact endothelial preparations, 5-HT (lO-s M)-induced contraction was markedly relaxed by the addition of ACh( IO-SM) and this endothelium-dependent relaxing effect was inhibited by atropine (l0-7M)-pretreatment but notaffected by diltiazem (l0-6M)-pretreatment. These results suggest that ACh elicits endotheliumdependent relaxing effect mediated by muscarinic receptors in cerebral arteries of pig and rabbit, and that ACh acts as vasoconstrictor in cat cerebral artery.

• Journal of Chest Surgery
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• v.24 no.7
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• pp.637-646
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• 1991

Effect of noradrenaline and endothelium on the high K+ or Ach-induced contraction were investigated in the pig myocardial coronary artery. The helical strip of isolated pig myocardial coronary artery was immersed in the Tris-buffered Tyrode`s solution equilibrated with 100% O2 at 37oC and its isometric tension was measured. High K+ and Ach-induced contraction were dose-dependent. By denuding the endothelium, dose-contraction curve of K+ was not shifted significantly to the left and upward, but that of Ach was shifted significantly to same direction 25 mM K+ - and Ach-induced contraction were relaxed by norepinephrine[NE]. NE-induced relaxation was blocked by the pretreatment of propranolol, which was known as b-adrenoceptor blocker. And, phenylephrine known as a-adrenoceptor agonist, and clonidine known as a-adrenoceptor agonist increased the 25mM K+ - induced contraction respectively. Denuding of endothelium did not show any significant effects on NE-induced relaxation and contraction increased by phenylephrine and clonidine. Tyramine increased 25mM K+ - induced contraction further. The contractile response by tyramine on the 25mM K+ - induced contraction was not blocked by the pretreatment of phentolamine, but was partially blocked by the pretreatment of atropine. From the above results, it is suggested that activation of a1-and a2-adrenoceptors induce the contraction, activation of b-adrenoceptors induce the relaxation, and NE-induced relaxation is mainly due to activation of b-adrenoceptors. Also it is suggested that denudation of endothelium did not influence NE-induced relaxation, but influence Ach-induced contraction in the pig myocardial coronary artery.