흰쥐 적출 대동맥에서 alpha1-수용체 효능약과 alpha2-수용체 효능약의 혈관수축반응에 대한 내피세포의 영향

정준기(Joon Ki Chung),홍승철(Sung Cheul Hong),최수경(Su Kyung Choi),강맹희(Maeng Hee Kang),구미경(Mi Geong Ku),박상일(Sang Il Park),윤일(Il Yun) 대한약학회 1990 약학회지 Vol.34 No.3

A comparison was made of the effects of selective alpha1-adrenoceptor agonist phenylephrine and selective alpha2-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 EC50 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 EC50 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 alpha1-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 alpha1-adrenoceptor with dibenamine.

Effect of Blood Pressure on the Endothelium-Dependent Contraction in Rat Aorta

Jeon. Byeong-Hwa,Kim. Hoe-Suk,Kim. Se-Hoon,Chang. Seok-Jong 대한생리학회 1996 대한생리학회지 Vol.30 No.1

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 ~ 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.

Altered Endothelial Modulation of Vasoconstriction in Chronic Two-Kidney, One Clip Hypertensive Rats

Jun, Jae-Yeoul,Yeum, Cheol-Ho,Moon, Sung-Ho,Cho, Cheol-Hee,Jun, Kyu-Bae,Chung, Jong-Hoon,Yoon, Pyung-Jin 대한신장학회 2001 대한신장학회잡지 Vol.20 No.3

Effect of Preconditioning Ischemia on Endothelial Dysfunction Produced by Ischemia-Reperfusion in Rabbit Coronary Artery

Suh. Suk-Hyo,Park. Yee-Tae,Kim. Woong-Heum,Kim. Ki-Whan 대한생리학회 1995 대한생리학회지 Vol.29 No.1

This study was designed to test whether or not 1) ischemia-reperfusion attenuates endothelium-dependent relaxation of coronary arteries and 2) preconditioning protects the arterial endothelium from ischemia-reperfusion injury. In anesthetized open chest rabbits, branches of the left circumflex artery were exposed to different combinations of the experimental conditions; ischemia (15 minutes), ischemia (15 minutes)-reperfusion (10 minutes), preconditioning ischemia, and pre-conditioning fellowed by ischemia-reperfusion. Preconditioning consisted of 3 occlusions of 2-min duration, each followed by n 5-min reperfusion. Rings of the artery exposed to the experimental condition and of normal left anterior descending coronary artery were prepared and suspended for isometric force measurement in organ chambers containing Krebs Ringer bicarbonate solution. The rings were contracted with 29.6 mM KCI. Ischemia alone did not attenuate endothelium-dependent relaxation by acetylcholine. However, ischemia-reperfusion significantly impaired endothelium-dependent relaxation. Endothelium-independent relaxation by sodium nitroprusside was not impaired by ischemia-reperfusion and the constrictive response to acetylcholine was not altered in reperfused rings without endothelium, compared with control rings. Arterial rings exposed to preconditioning followed by ischemia-reperfusion exhibited impaired endothelium-dependent relaxation by acetyl-choline. However, although preconditioning not fellowed by ischemia-reperfusion, attenuated endothelium-dependent relaxation at low concentrations of acetylcholine, the magnitude of the impairment by preconditioning followed by ischemia-reperfusion was significantly less than that of the impairment by ischemia-reperfusion alone. These data demonstrate that ischemia-reperfusion significantly attenuates endothelium-dependent relaxation by producing endothelial dysfunction and preconditioning Protects the endothelium of coronary arteries from ischemia-reperfusion injury.

관동맥의 내피세포의존성 혈관이완에 대한 마그네슘의 영향

송재관(Jae Kwan Song),고문수(Moon Soo Koh),염광섭(Kwang Seoup Yeoum),이진오(Jhin Oh Lee),강태웅(Tae Woong Kang),서정돈(Jung Don Seo),이영우(Young Woo Lee),서석효(Suk Hyo Suh),김기환(Ki Whan Kim) 대한내과학회 1990 대한내과학회지 Vol.39 No.4

N/A After the historical discovery of a soluble vasodilating substance from the vascular endothelium (endothelium-derived relaxing factor, EDRF), impaired EDRF-mediated vasorelaxation is discussed as one of the main pathogenic mechanisms of coronary artery spasm. Recently, some clinical reports that hypomagnesemia may be implicated in the induction of coronary artery spasm were presented, although there are controversial reports on the effects of the extracellular magnesium ion on endothelium-dependent vasorelaxation. Isometric contraction-relaxation was recorded in the transverse strips of porcine coronary artery to clarify the exact effects of Mg2+ on tension-development by a vasoconstrictor agent and on endothelium-dependent vasorelaxation and to predict a possible mechanism of hypomagnesemia in the induction of coronary artery spasm. The results of our study were as follows: 1) Vasoconstrictor activity of PGF2α was significantly more attenuated in the endothelium-intact transverse strips of porcine coronary artery than in the endothelium-denuded strips. 2) Lowering the magnesium concentration enhanced the vasoconstrictor activity of PGF2α while a marked reduction of isometric tension was observed with the elevation of magnesium concentration. 3) Bradykinin-induced endothelium-dependent vasorelaxation is a dose-dependent manner which was completely abolished with the pretreatment of hemoglobin. 4) Endothelium-dependent vasorelaxation of bradykinin was markedly inhibited by lowering the extracellular calcium ion concentration. 5) Change of the extracellular magnesium ion concentration did not alter the IC50 (inhibitory concentration of bradykinin causing a 50% inhibition of the maximum contraction) values of bradykinin-induced endothelium dependent vasorelaxation. From these results it is concluded that if magnesium deficiency is implicated in the induction of coronary artery spasm, the main mechanism would be direct enhancement of responsiveness of the vascular smooth muscle to the vasoconstrictors. Further study with a bioassay system and more various stimulators of EDRF secretion is necessary for exact clarification of the effects of Mg2+ on endothelium-dependent vasorelaxation.

Endothelium-derived Relaxing Factors of Small Resistance Arteries in Hypertension

Kyu-Tae Kang 한국독성학회 2014 Toxicological Research Vol.30 No.3

Endothelium-derived relaxing factors (EDRFs), including nitric oxide (NO), prostacyclin (PGI2), and endothelium-derived hyperpolarizing factor (EDHF), play pivotal roles in regulating vascular tone. Reduced EDRFs cause impaired endothelium-dependent vasorelaxation, or endothelial dysfunction. Impaired endothelium-dependent vasorelaxation in response to acetylcholine (ACh) is consistently observed in conduit vessels in human patients and experimental animal models of hypertension. Because small resistance arteries are known to produce more than one type of EDRF, the mechanism(s) mediating endothelium-dependent vasorelaxation in small resistance arteries may be different from that observed in conduit vessels under hypertensive conditions, where vasorelaxation is mainly dependent on NO. EDHF has been described as one of the principal mediators of endothelium-dependent vasorelaxation in small resistance arteries in normotensive animals. Furthermore, EDHF appears to become the predominant endothelium-dependent vasorelaxation pathway when the endothelial NO synthase (NOS3)/NO pathway is absent, as in NOS3-knockout mice, whereas some studies have shown that the EDHF pathway is dysfunctional in experimental models of hypertension. This article reviews our current knowledge regarding EDRFs in small arteries under normotensive and hypertensive conditions.

Endothelium-dependent Contraction of Aorta in One-kidney, One-clip Goldblatt Hypertensive Rat

Jeon, Byeong-Hwa,Lee, Kug-Hee,Kim, Hoe-Suk,Kim, Se-Hoon,Chang, Seok-Jong The Korean Physiological Society 1996 대한생리학회지 Vol.30 No.2

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.

Differential role of endothelium in hawthorn fruit extract-induced relaxation of rat cerebral, coronary, carotid, and aorta

Chan, Hoi Yun,Chen, Zhen-Yu,Yao, Xiaoqiang,Lau, Chi-Wai,Zhang, ZeSeng,Ho, Walter Kwok Keung,Huang, Yu Kyung Hee Oriental Medicine Research Center 2002 Oriental pharmacy and experimental medicine Vol.2 No.2

The present study was aimed to examine the role of endothelium in the relaxant effect of hawthorn fruit extract of Crataegus pinnatifida in four different types of rat arteries, posterior cerebral communicating artery, right descending coronary artery, common carotid artery, and aorta. In $9,11-dideoxy-11{\alpha}$, $9{\alpha}-epoxy-methanoprostaglandin$ $F_{2{\alpha}}$ (U46619)-preconstricted arterial rings except for aorta, the extract produced endothelium-independent relaxations with similar potency. This relaxation was unaffected by pretreatment with $100\;{\mu}M\;N^G-nitro-L-arginine$ methylester (L-NAME, the nitric oxide synthase inhibitor), $3\;{\mu}M$ 1H-[l,2,4]oxadiazolo$[4,2-{\alpha}]$quinoxalin-1-one (ODQ, the guanylate cyclase inhibitor), or $10\;{\mu}M$ indomethacin (the cyclooxygenase inhibitor). Putative $K^+$ channel blockers (charybdotoxin plus apamin or glibenclamide) did not affect the extract-induced relaxation in cerebral or coronary artery rings. In contrast, in rat aortic rings the extract produced significantly smaller relaxant response in endothelium-denuded rings than that in endothelium-intact rings. Pretreatment with L-NAME or ODQ abolished the extractinduced endothelium-dependent aortic relaxation, whilst indomethacin $(3\;{\mu}M)$ had no effect. The present results indicate that hawthorn fruit extract possesses a vasorelaxing effect in cerebral, coronary and carotid arteries and this effect is independent of the presence of a functional endothelium. However, the extract-induced endothelium-dependent relaxation in rat aorta was mediated through endothelial nitric oxide and cyclic GMP-dependent mechanisms, suggesting that active components in the extract may act on endothelium to stimulate release of nitric oxide in large conduit arteries of the rats.

혈관내피세포 유무에 따른 돼지 관동맥에서의 Endothelin에 대한 반응

홍명기,김재중,이철환,박성욱,박승정 대한순환기학회 1998 Korean Circulation Journal Vol.28 No.12

Endothelium-derived Relaxing Factors of Small Resistance Arteries in Hypertension

강규태 한국독성학회 2014 Toxicological Research Vol.30 No.3

Endothelium-derived relaxing factors (EDRFs), including nitric oxide (NO), prostacyclin (PGI2), and endothelium-derivedhyperpolarizing factor (EDHF), play pivotal roles in regulating vascular tone. Reduced EDRFs cause impaired endothelium-dependent vasorelaxation, or endothelial dysfunction. Impaired endothelium-dependent vasorelaxation in response to acetylcholine (ACh) isconsistently observed in conduit vessels in human patients and experimental animal models of hypertension. Because smallresistance arteries are known to produce more than one type of EDRF, the mechanism(s) mediating endothelium-dependentvasorelaxation in small resistance arteries may be different from that observed in conduit vessels under hypertensive conditions,where vasorelaxation is mainly dependent on NO. EDHF has been described as one of the principal mediators of endothelium-dependent vasorelaxation in small resistance arteries in normotensive animals. Furthermore, EDHF appears to become thepredominant endothelium-dependent vasorelaxation pathway when the endothelial NO synthase (NOS3)/NO pathway is absent, as in NOS3-knockout mice, whereas some studies have shown that the EDHF pathway is dys-functional in experimental models ofhypertension. This article reviews our current knowledge regarding EDRFs in small arteries under normotensive and hypertensiveconditions.