• Archives of Pharmacal Research
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• 제28권6호
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• pp.709-715
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• 2005

The purpose of this study was to investigate the effect of atropine on peripheral vasodilation and the mechanisms involved. The isometric tension of rat mesenteric artery rings was recorded in vitro on a myograph. The results showed that atropine, at concentrations greater than 1$\mu$M, relaxed the noradrenalin (NA)-precontracted rat mesenteric artery in a concentration-dependent manner. Atropine-induced vasodilatation was mediated, in part, by an endothelium-dependent mechanism, to which endothelium-derived hyperpolarizing factor may contribute. Atropine was able to shift the NA-induced concentration-response curve to the right, in a non-parallel manner, suggesting the mechanism of atropine was not mediated via the ${\alpha}_1$-adrenoreceptor. The $\beta$-adrenoreceptor and ATP sensitive potassium channel, a voltage dependent calcium channel, were not involved in the vasodilatation. However, atropine inhibited the contraction derived from NA and $CaCl_2$ in $Ca^{2+}$-free medium, in a concentration dependent manner, indicating the vasodilatation was related to the inhibition of extracellular $Ca^{2+}$ influx through the receptor-operated calcium channels and intracellular $Ca^{2+}$ release from the $Ca^{2+}$ store. Atropine had no effect on the caffeine-induced contraction in the artery segments, indicating the inhibition of intracellular $Ca^{2+}$ release as a result of atropine most likely occurs via the IP3 pathway rather than the ryanodine receptors. Our results suggest that atropine-induced vasodilatation is mainly from artery smooth muscle cells due to inhibition of the receptor-mediated $Ca^{2+}$-influx and $Ca^{2+}$-release, and partly from the endothelium mediated by EDHF.

• Journal of Chest Surgery
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• 제31권2호
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• pp.102-107
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• 1998

L-Arginine이 산화질소 생성의 전구물질로서 공헌하는 것 이외에 다른 기전에 의하여도 혈관이완을 일으키는가 구명하기 위하여 적출 흰쥐 흉부대동맥 표본에서 L-arginine에 의한 장력, 조직 산화질소 및 cGMP 함량 변동 등을 조사하여 다음과 같은 결과를 얻었다. 1. Phenylephrine(3.5$\times$10－6 mol/L) 수축 대동맥 표본은 L-arginine(10－9~10－3 mol/L)에 의해 용량의존 이완되었다. NG-Nitro-L-arginine methyl ester(L-NAME, 10－5 mol/L) 전처치에 의해 저농도 L-arginine(10－9~10－6 mol/L)에 혈관이완 효과는 소실되었으나 고농도 L-arginine(10－4~10－3 mol/L)의 이완효과는 도리어 증강되었다. 내피층 파괴 혈관 표본은 L-arginine에 대해 이완반응을 보이지 않았다. 2. L-NAME(10－5 mol/L) 존재하에 일어나는 L-arginine 이완효과는 indomethacin 전처치에 의해 영향받지 않으나, ouabain 전처치에 의해 유의하게 감약되었다. 또한 L-arginine 이완효과는 methylene blue에 의해 부분적으로 길항되었다. KCl(3.5$\times$10－2 mol/L) 수축 대동맥 표본은 L-arginine(10－9~10－3 mol/L)에 의해 L-NAME (10－5 mol/L) 처치와 무관하게 이완반응을 보이지 않았다. 3. L-NAME는 혈관조직 산화질소 함량을 감소시키며 이 감소효과는 L-arginine(10－4 mol/L)에 의해 영향받지 않았다. 또한 L-NAME는 혈관조직 cGMP 함량을 감소시키나 이 감소효과는 L-arginine에 의해 영향받지 않았다. 이상의 실험성적은 L-arginine이 내피세포의 산화질소 및 cGMP 생성과 무관한 기전을 통해서도 내피의존 혈관이완효과를 나타냄을 시사하였다.

• 동의생리병리학회지
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• 제21권2호
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• pp.408-413
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• 2007

Vascular tone plays an important role in the regulation of blood pressure. In the present study, the methanol extract of Rosae multiflora Radix (MRM) induced dose-dependent relaxation of phenylephrine-precontracted aorta, which was abolished by removal of functional endothelium. Pretreatment of the endothelium-intact aortic tissues with $N^G$-nitro-L-arginine methly ester (L-NAME) or 1H-[1,2,4]-oxadiazole-[4,3-${\alpha}$]-quinoxalin-1-one (ODQ) inhibited the relaxation induced by MRM, respectively. But, the relaxation effect of MRM was not blocked by indomethacine, glibenclamide, tetraethylammonium (TEA), verapamil, diltiazem, atropine, and propranolol, respectively. Moreover, incubation of endothelium-intact aortic rings with MRM increased the production of cGMP. Taken together, the present results suggest that MRM relaxes vascular smooth muscle via endothelium-dependent nitric oxide/cGMP signaling. These results would be useful for further study to MRM on animal models with cardiovascular diseases.

• Tuberculosis and Respiratory Diseases
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• 제41권3호
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• pp.231-238
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• 1994

연구배경: 저산소증에 의한 폐동맥수축의 기전은 저산소증 자체가 폐혈관 평활근에 직접 작용하여 수축을 유발한다는 것과, 저산소증에 의해 조직으로 부터 여러 매개물질이 유리되어 혈관평활근을 수축시킨다는 설이 제시되고 있지만 정확히 밝혀져있지 않다. 최근에는 저산소증이 EDRF의 생성을 억제하여 혈관수축을 유발시킨다고하여 관심이 되고 있다. 본 연구에서는 흰쥐 폐동맥에서 내피세포 의존형 혈관이완을 조사하고, 저산소증에 의한 폐동맥수축에 EDRF의 작용을 조사하였다. 방법 : 300~350g의 수컷 흰쥐(Sprague Dawley)의 폐동맥을 박리하여 길이가 2mm되는 폐동맥고리를 Krebs용액으로 채워져 있으며, 95% $O_2$/5% $CO_2$(산소상태)와 95% $N_2$/5% $CO_2$(저산소상태)가 각각 공급되는 magnus관에서 가는 stainless 갈고리로 고정한 다음 Gilson사의 polygraph에 부착된 isometric transducer(FT.03 Grass, Quincy, USA)에 의해 등장성 수축곡선을 그리도록 장치하였다. 결과: 1) 내피세포가 있는 폐동맥에서 PE($10^{-6}M$)에 의한 혈관수축은 Ach($10^{-9}-10^{-5}M$) 및 SN($10^{-9}-10^{-5}M$)의 농도에 비례해서 이완되어 거의 기초장력까지 이완되었으나, 내피세포를 제거한 폐동맥에서는 Ach($10^{-9}-10^{-5}M$)에 의한 혈관이완은 거의 상실되었다. 2) L-NMMA($10^{-4}M$)으로 전처치한 경우 Ach($10^{-9}-10^{-5}M$)에 의한 혈관이완은 전처치하지 않은 경우보다 의미있게 감소하였다. 3) L-arginine($10^{-4}M$)과 L-NMMA($10^{-4}M$)을 전처치 하였을 경우 Ach($10^{-9}-10^{-5}M$)에 의한 혈관이완은 L-NMMA에 의해 거의 영향을 받지 않았다. 4) PE($10^{-6}M$)에 의한 폐동맥 수축은 산소상태보다 저산소 상태에서 훨씬 강했으며, Ach($10^{-9}-10^{-5}M$)에 의한 혈관이완은 산소상태보다 저산소상태에서 의미있게 감소하였다. 5) L-arginine($10^{-4}M$)을 전처치 하였을 경우 저산소상태에서의 Ach($10^{-9}-10^{-5}M$)에 의한 혈관이완은 산소상태에서의 Ach 에 의한 혈관이완 정도로 회복되었다. 결론: 흰쥐 폐동맥에서 내피세포의존성 혈관이완은 NO가 관여하며, 저산소증에 의한 폐동맥 수축은 내피세포내의 EDRF 생성의 저하와 관련이 있을 것으로 사료된다.

• 대한본초학회지
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• 제25권4호
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• pp.17-21
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• 2010

Objectives : The aim of this study was to evaluate the differential mechnism of vasodilation of alcohol steamed Rhei Tangutici Radix et Rhizoma. (ART) and Rhei Tangutici Radix et Rhizoma. (RT) in rat thoracic aorta. Methods : Rat aortic ring preparations were mounted in organ baths with oxygenated (95% $O_2$-5% $CO_2$) Krebs-Ringer bicarbonate solutions at $37{\pm}0.5^{\circ}C$ and subjected to contractions or relaxations. Results : ART exerted vasorelaxation on phenylephrine(PE)-induced contraction in a dose dependent manner. Vasorelaxation effects of ART and RT were endothelium-independent. In the $Ca^{2+}$-free high KCl (60 mM) baths, the contraction of aortic rings induced by accumulative addition of $Ca^{2+}$ (0.3-10.0 mM) was significantly reduced by pre-treatment with both ART and RT for 10 min. The magnitude of vasodilatation was biggerin ART. Moreover, verapamil ($0.001{\mu}M$) and diltiazem ($10{\mu}M$), voltage operative $Ca^{2+}$channel blockers, attenuated the relaxation effect of ART but not that of RT. In the absence of extracellular $Ca^{2+}$, pre-incubation of the aortic rings with RT ($1.0mg/m{\ell}$) significantly reduced the contraction caused by PE but not that of ART. $K^+$ channel inhibitors such as glibenclamide (Gli, $10^{-5}M$), tetraethylammonium (TEA, 1 mM) and 4-aminopyridine (4-AP, 0.2 mM) significantly reduced the ART's vasorelaxation efficacy, but not that of RT. However, the relaxation effects of ART and RT were not inhibited by pre-treatment with indomethacin ($10^{-5}M$), and atropine ($10^{-6}M$). Conclusions : These results suggest that the endothelium-independent relaxation is due to inhibition of $Ca^{2+}$ influx via the suppression of $Ca^{2+}$ release from intracelluar store in RT but via both voltage operative $Ca^{2+}$channel blockage and $K^+$ channel activation in ART.

• The Korean Journal of Physiology and Pharmacology
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• 제14권3호
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• pp.177-183
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• 2010

Tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthase (NOS) activity, is known to play important roles in modulating both NO and superoxide production during vascular diseases such as atherosclerosis. However, the role of BH4 in functions of vascular smooth muscle cells is not fully known. In this study, we tested the effects of BH4 and dihydrobiopterin (BH2), a BH4 precursor, on migration and proliferation in response to platelet-derived growth factor-BB (PDGF-BB) in rat aortic smooth muscle cells (RASMCs). Cell migration and proliferation were measured using a Boyden chamber and a 5-bromo-2'-deoxyuridine incorporation assay, respectively, and these results were confirmed with an ex vivo aortic sprout assay. Cell viability was examined by 2,3-bis [2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide assays. BH4 and BH2 decreased PDGF-BBinduced cell migration and proliferation in a dose-dependent manner. The inhibition of cell migration and proliferation by BH4 and BH2 was not affected by pretreatment with $N^G$-nitro-L-arginine methyl ester, a NOS inhibitor. Moreover, the sprout outgrowth formation of aortic rings induced by PDGF-BB was inhibited by BH4 and BH2. Cell viability was not inhibited by BH4 and BH2 treatment. The present results suggest that BH4 and BH2 may inhibit PDGF-stimulated RASMC migration and proliferation via the NOS-independent pathway. Therefore, BH4 and its derivative could be useful for the development of a candidate molecule with an NO-independent anti-atherosclerotic function.

• 약학회지
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• 제43권2호
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• pp.237-250
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• 1999

In order to investigate the pharmacologic properties of New Wonbang Woohwangchungsimwon Pill(NSCH), effects of Wonbang Woohwangchungsimwon Pill (SCH) and NSCH were compared using various experimental models. In rat aorta, NSCH and SCH made the relaxation of blood vessels in maximum contractile response to phenylephrine (10-6 M) regardless to endothelium containing or denuded rings of the rat aorta. Furthermore, the presence of the inhibitors of NO synthase and guanylate cyclase did not affect significantly the relaxing effects of NSCH and SCH. NSCH and SCH inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NSCH and SCH decreased significantly heart rate. These, at high doses, had a negative inotropic effects that was a decrease of left ventricular developed pressure and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In guinea-pig papillary muscle, these had no effects on parameters of action potential such as action potential amplitude (APA), $V_{max}$ and resting membrane potential (RMP) at low doses, whereas inhibitory the cardiac contractility at high doses. Furthermore, these had a significant inhibitory effects on palpitation of the heart in normotensive rats and SHRs. These had a significant inhibitory effects on palpitation of the heart in normotensive rats and SHRs. These results suggest that NSCH and SCH have weak cardiovascular effects, and that there is no significant differences between cardiovascular effects of two preparations.

• The Korean Journal of Physiology and Pharmacology
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• 제21권6호
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• pp.617-623
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• 2017

The vascular actions and mechanisms of taurine were investigated in the isolated human radial artery (RA). RA rings were suspended in isolated organ baths and tension was recorded isometrically. First, a precontraction was achieved by adding potassium chloride (KCl, 45 mM) or serotonin (5-hydroxytryptamine, 5-HT, $30{\mu}M$) to organ baths. When the precontractions were stable, taurine (20, 40, 80 mM) was added cumulatively. Antagonistic effect of taurine on calcium chloride ($10{\mu}M$ to 10 mM) -induced contractions was investigated. Taurine-induced relaxations were also tested in the presence of the $K^+$ channel inhibitors tetraethylammonium (1 mM), glibenclamide ($10{\mu}M$) and 4-aminopyridine (1 mM). Taurine did not affect the basal tone but inhibited the contraction induced by 5-HT and KCl. Calcium chloride-induced contractions were significantly inhibited in the presence of taurine (20, 40, 80 mM) (p<0.05). The relaxation to taurine was inhibited by tetraethylammonium (p<0.05). However, glibenclamide and 4-aminopyridine did not affect taurine -induced relaxations. Present experiments show that taurine inhibits 5-HT and KCl -induced contractions in RA, and suggest that large conductance $Ca^{2+}$-activated $K^+$ channels may be involved in taurine -induced relaxation of RA.

• 생명과학회지
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• 제16권7호
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• pp.1141-1147
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• 2006

녹두 유식물체 줄기를 조직배양하여 캘러스조직을 형성하였고 이로부터 부정아 형성을 유도한 다음, 캘러스 조직과 부정아 분화에 대한 기원을 조직해부학적으로 연구하였다. 녹두 줄기절편으로부터 캘러스조직의 유도는 0.5 mg/L 2,4-D와 1.0 mg/L kinetin이 첨가된 MS배지가 효과적이었고, 캘러스로부터의 부정아 분화에는 0.75 mg/L NAA와 1.5 mg/L kinetin이 첨가된 MS배지가 매우 효과적이어서 약 21%의 기관형성율을 나타내었다. 캘러스 조직을 조직 학적으로 관찰한 결과, 캘러스조직은 유관속 형성층 외측에 새롭게 형성된 분열능력이 있는 캘러스 형성층환인_바깥쪽으로 생장을 함으로써 유도되었다. 부정아는 캘러스 조직의 외부 표면부위에서 기원된 부정아 정단분열조직으로부터 발생되었다. 부정아 정단분열조직은 엽원기를 형성하여 나중에 잎이 발생되었다.

• The Korean Journal of Physiology
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• 제30권1호
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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.