• 산업융합연구
• /
• 제21권10호
• /
• pp.57-63
• /
• 2023

평활근 수축에 대한 감초산(glycyrrhizic acid)의 효과를 연구하고자 하였고 관련 상세 기전을 결정하기 위해 glycyrrhizic acid가 agonist-sensitive하게 평활근 수축한다는 가설을 제시하였다. S/D rats의 평활근을 수조 내 준비하였고 신호 변환기에서 평활근에 의한 운동 신호가 전기적 신호로 변환되어 생리기록기에 표시되는 데이터는 일원배치 분산분석으로 분석하였다. 재미있게도, 감초산은 불화물, 트롬복산 유사체 등 굵은 미세섬유성 조절성 수축제에 의한 평활근 수축을 중등도로 억제하였고 (농도 0.01, 0.03, 0.1 mM 불화물에서 p=0.113, 0.008, 0.004 (Student's t-test), p=0.113, 0.008, 0.004 (One way ANOVA), 그리고 0.01, 0.03, 0.1 mM 트롬복산 유사체에서 p=0.156, 0.004, 0.003 (Student's t-test), p=0.156, 0.004, 0.003 (One way ANOVA)) 포볼 에스테르 등 가는 미세섬유성 조절성 수축제에 의한 평활근 수축에 대해 효과가 소실되었다 (0.01, 0.03, 0.1 mM 포볼 에스테르에서 p=0.392, 0.086, 0.065 (Student's t-test), p=0.392, 0.086, 0.065 (One way ANOVA)). 이러한 결과는 내피 기능이 억제된 평활근에서 감초산은 평활근 내피에서 EDRF (NO) 생성 효과 외에 주로 ROCK 활성 감소 등 평활근에 대한 직접적 효과를 통해 최종적으로 평활근에서 악틴-미오신 상호작용을 제한하여 평활근을 이완시키는 것으로 생각된다.

• 약학회지
• /
• 제51권5호
• /
• pp.301-306
• /
• 2007

Rosiglitazone ($Avandia^{(R)}$) represents a new class of antidiabetic drugs which are $PPAR{\gamma}$ agonists. The present study was undertaken to determine whether the new antidiabetic rosiglitazone influences on the agonist-induced regulation of vascular smooth muscle contraction as an antihypertensive and, if so, to investigate the related mechanism. Endothelium-denuded arterial rings from male Sprague-Dawley rats were used and isometric contractions were recorded using a computerized data acquisition system. Rosiglitazone decreased Rho-kinase activating agonist (NaF or thromboxane $A_2$ mimetic)-induced contraction but not depolarization- or phorbol ester-induced contraction. Surprisingly, it slightly potentiated the latter contraction possibly opening a voltage-dependent calcium channel by its chemical structure on 50 mM KCI- or $1{\mu}M$ phorbol 12,13-dibutyrate-induced vasoconstriction. In conclusion, this study provides the evidence and possible related mechanism concerning the biphasic effect of an antidiabetic rosiglitazone as a possible antihypertensive on the agonistinduced contraction in rat aortic rings regardless of endothelial function.

• 대한약리학회지
• /
• 제24권2호
• /
• pp.197-201
• /
• 1988

본 연구에서는 세포내의 칼슘이온과 결합하여 형광을 발하는 형광색소 fura 2를 이용하여 세포내의 칼슘이은 농도를 측정함과 동시에 장력을 측정하였으며 이에 대한 카페인과 고농도의 칼륨의 영향을 정토하였다. 72.7 mM의 칼륨 이온은 장력과 세포내 칼슘이온농도에서 각각 지속적 인 증가를 보여주었으며, 20 mM의 카페인은 일과성의 빠른 세포내의 칼슘이은농도의 증가에 이어 감소를 보여주었으나 기본치 보다는 높았다. 그러나, 장력에 있어서는 카페인은 일과성의 증가에 이어 기본 장력보다 낮은 감소를 보여주었다. 한편 칼슘이온 제거 용액에서 칼륨이온은 세포내의 갈륨이온 농도도 장력도 증가 시키지 못하였으나 카페인은 일과성의 세포내의 칼륨이온 농도와 장책의 증가를 보여주었다. 이상과 결과로부터 rat 대동맥에서의 고농도의 칼륨이은에 의한 수축은 세포 딴으로 부터의 칼슘이온 유입에 의한 것이며 반면에 카페인에 의한 수축은 세포내의 칼슘이온저장부위로 부터의 칼슘이온 유리에 의한 것임을 시사한다. 또한, 카페인은 세포내의 수축 단백의 칼슘 이온에 대한 감수성을 저하시키는 듯하다.

• 약학회지
• /
• 제50권4호
• /
• pp.293-299
• /
• 2006

The aim of present study was to investigate the possible influence of Rho-kinase inhibition on the plant-derived estrogen-like compounds-induced arterial relaxation. Agonist- or depolarization-induced vascular smooth muscle contractions involve the activation of Rho-kinase pathway. However there are no reports addressing the question whether this pathway is involved in genistein-or daidzein-induced vascular relaxation in rat aortae precontracted with phenylephrine or thromboxane $A_2$ mimetic U-46619. We hypothesized that Rho-kinase inhibition plays a role in vascular relaxation evoked by genistein or daidzein in rat aortae. Endothelium-intact and denuded arterial rings from male Sprague-Dawley rats were used and isometric contractions were recorded using a computerized data acquisition system. Genistein concentration-dependently inhibited phenylephrine or thromboxane $A_2-induced$ contraction regardless of endothelial function. Surprisingly, in the agonists-induced contraction, similar results were also observed in aortae treated with daidzein, the inactive congener for protein tyrosine kinase inhibition, suggesting that Rho-kinase might act upstream of tyrosine kinases in phenylephrine-induced contraction. In conclusion, in the agonists-precontracted rat aortae, genistein and daidzein showed similar relaxant response regardless of tyrosine kinase inhibition or endothelial function.

• Biomolecules & Therapeutics
• /
• 제7권3호
• /
• pp.221-226
• /
• 1999

In this study, 75% ethanol extract from the flowers of Carthamus tinctorius was prepared and biological activities were examined. The extract showed the inhibitory activity of vascular smooth muscle contraction and antithrombotic activity judged by bleeding time measurement. It also showed anti-inflammatory and potent analgesic activities in vivo. By oral administration of the extract, no acute toxicity was observed up to 5 g/kg in mice and rats. All these results strongly suggest that this extract may be beneficial for postmenopausal disorder by enhancing blood circulation.

• Biomolecules & Therapeutics
• /
• 제16권3호
• /
• pp.249-254
• /
• 2008

The present study was undertaken to determine whether hypoxia influences on the agonist-induced vascular smooth muscle contraction and, if so, to investigate the related mechanism. The measurement of isometric contractions using a computerized data acquisition system was combined with molecular experiments. Hypoxia significantly inhibited fluoride-induced contraction regardless of endothelial function, but there was no relaxation on thromboxane $A_2$ mimetic U-46619-induced contraction suggesting that other pathway such as $Ca^{2+}$ entry or thin filament regulation was not affected. In addition, hypoxia significantly decreased fluoride-induced increase of phospho-myosin-targeting subunit of myosin light chain phosphatase (pMYPT1). Interestingly, hypoxia didn't inhibit significantly phenylephrine-induced contraction suggesting that myosin light chain kinase (MLCK) activity or thin filament regulation is less important on the hypoxia-induced vasorelaxation in the denuded muscle than Rho-kinase activity. In conclusion, this study provides the evidence and possible related mechanism concerning the vasodilation effect of hypoxia on the agonist-specific contraction in rat aortic rings regardless of endothelial function.

• Biomolecules & Therapeutics
• /
• 제20권3호
• /
• pp.352-356
• /
• 2012

The present study was undertaken to determine whether ethanol influences on the agonist-induced vascular smooth muscle contraction and, if so, to investigate the related mechanism. The measurement of isometric contractions using a computerized data acquisition system was combined with molecular experiments. Ethanol significantly inhibited thromboxane $A_2$ mimetic-induced contraction with intact endothelial function, but there was no relaxation on thromboxane $A_2$ mimetic U-46619-induced contraction irrespective of endothelium suggesting that the pathway such as Rho-kinase activation, $Ca^{2+}$ entry or thin filament regulation was not affected. In addition, ethanol didn't decrease thromboxane $A_2$ mimetic-induced increase of phospho-myosin phosphatase targeting subunit protein 1 (pMYPT1) or pERK1/2. Interestingly, ethanol didn't inhibit significantly phorbol ester-induced contraction in denuded muscles suggesting that thin filament regulation is less important on the ethanol-induced regulation in the muscle than endothelial NO synthesis. In conclusion, this study provides the evidence and possible related mechanism concerning the effect of ethanol on the agonist-dependent contraction in rat aortic rings with regard to endothelial function.

• The Korean Journal of Physiology
• /
• 제24권2호
• /
• pp.281-291
• /
• 1990

The $Ca^{2+}-substitutional$ roles of strontium for the contractile processes were investigated in the rabbit renal artery. The contractions induced by either norepinephrine or high $K^+$ in the condition which intra- and extracellular $Ca^{2+}$ were replaced by $Sr^{2+}$, i.e. $Sr^{2+}-mediated$ contractions, were dose-dependent. And then the maximal amplitude of contraction, as compared with $Ca^{2+}-mediated$ contraction, was about 50% in norepinephrine and about 70% in high $K^+$. The $Sr^{2+}-mediated$ contractions were independent in the contraction by norepinephrine $(10^{-5}M)$ but dependent in those by high $K^+(100\;mM)$ on the extracellular $Sr^{2+}$ concentration. Also $Sr^{2+}-mediated$ contractions induced by norepinephrine were observed in the $Sr^{2+}-free$ Tyrode's solution. The $Sr^{2+}-mediated$ contractions induced by either norepinephrine or high $K^+$ were suppressed by verapamil, a $Ca^{2+}-channel$ blocker. By extracellular addition of $Sr^{2+}$, the $Ca^{2+}-mediated$ contractions induced by norepinephrine $(10^{-5}M)$ or 40 mM $K^+$ were inhibited but those by high $K^+(100\;mM)$ were increased. And the $Sr^{2+}-mediated$ contractions were increased by extracellular addition of $Ca^{2+}$ but did not reach the level of $Ca^{2+}-mediated$ contraction. Therfore it is suggested that in the vascular smooth muscle of rabbit renal artery $Sr^{2+}$ could enter the smooth muscle cells easily through the potential-operated calcium channel (POC) but not easily through the receptor-operated calcium channel (ROG), and $Sr^{2+}$ might be stored in the intracellular $Ca^{2+}-binding$ site and released by NE and induced the contraction by a way of activating directly the contractile apparatus.

• Molecules and Cells
• /
• 제27권2호
• /
• pp.191-198
• /
• 2009

The present study was undertaken to determine whether treatment with genistein, the plant-derived estrogen-like compound influences agonist-induced vascular smooth muscle contraction and, if so, to investigate related mechanisms. The measurement of isometric contractions using a computerized data acquisition system was combined with molecular experiments. Genistein completely inhibited KCl-, phorbol ester-, phenylephrine-, fluoride- and thromboxane $A_2$-induced contractions. An inactive analogue, daidzein, completely inhibited only fluoride-induced contraction regardless of endothelial function, suggesting some difference between the mechanisms of RhoA/Rho-kinase activators such as fluoride and thromboxane $A_2$. Furthermore, genistein and daidzein each significantly decreased phosphorylation of MYPT1 at Thr855 had been induced by a thromboxane $A_2$ mimetic. Interestingly, iberiotoxin, a blocker of large-conductance calcium-activated potassium channels, did not inhibit the relaxation response to genistein or daidzein in denuded aortic rings precontracted with fluoride. In conclusion, genistein or daidzein elicit similar relaxing responses in fluoride-induced contractions, regardless of tyrosine kinase inhibition or endothelial function, and the relaxation caused by genistein or daidzein was not antagonized by large conductance $K_{Ca}$-channel inhibitors in the denuded muscle. This suggests that the RhoA/Rho-kinase pathway rather than $K^+$- channels are involved in the genistein-induced vasodilation. In addition, based on molecular and physiological results, only one vasoconstrictor fluoride seems to be a full RhoA/Rho-kinase activator; the others are partial activators.

• 약학회지
• /
• 제58권4호
• /
• pp.223-228
• /
• 2014

The present study was undertaken to investigate the influence of sulforaphane on vascular smooth muscle contractility and to determine the mechanism involved. We hypothesized that sulforaphane, the primary ingredient of broccoli of cruciferous vegetables, plays a role in vascular relaxation through inhibition of Rho-kinase in rat aortae. Intact of denuded arterial rings from male Sprague-Dawley rats were used and isometric tensions were recorded using a computerized data acquisition system. Interestingly, sulforaphane significantly inhibited fluoride, phorbol ester or thromboxane $A_2$ mimetic-induced contraction in denuded muscles suggesting that additional pathways different from endothelial nitric oxide synthesis such as inhibition of Rho-kinase or MEK might be involved in the vasorelaxation. Furthermore, sulforaphane inhibited thromboxane $A_2$-induced increases in pERK1/2 levels suggesting the mechanism including inhibition of thromboxane $A_2$-induced increases in ERK1/2 phosphorylation. This study provides evidence that sulforaphane induces vascular relaxation through inhibition of Rho-kinase or MEK in rat aortae.