• Journal of Industrial Convergence
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• v.21 no.10
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• pp.57-63
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• 2023

This study aims to elucidate the effect of glycyrrhizic acid on smooth muscle contraction and to determine the detailed mechanism incorporated. We hypothesized that glycyrrhizic acid played a role in the agonist-sensitive management of smooth muscle contraction. Stripped smooth muscles of Sprague-Dawley rats were prepared in organ baths and isometric tensions were converted, stored and analyzed by using isometric transducers, a physiograph and one way ANOVA. Interestingly, glycyrrhizic acid attenuated the thick filament regulating agonist (fluoride or thromboxane mimetic)-sensitive contraction (p=0.113, 0.008, 0.004 (Student's t-test), p=0.113, 0.008, 0.004 (One way ANOVA) at 0.01, 0.03, 0.1 mM fluoride, and p=0.156, 0.004, 0.003 (Student's t-test), p=0.156, 0.004, 0.003 (One way ANOVA) at 0.01, 0.03, 0.1 mM thromboxane mimetic) and did not attenuate the thin filament regulating agonist (phorbol ester)-induced contraction (p=0.392, 0.086, 0.065 (Student's t-test), p=0.392, 0.086, 0.065 (One way ANOVA) at 0.01, 0.03, 0.1 mM phorbol ester). It is suggesting that endothelial EDRF (NO) synthesis and accessory pathways besides endothelial EDRF (NO) synthesis such as ROCK restriction might be incorporated in the glycyrrhizic acid-induced modulation of smooth muscle contraction inhibiting acto-myosin interaction.

• YAKHAK HOEJI
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• v.51 no.5
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• pp.301-306
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• 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.

• The Korean Journal of Pharmacology
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• v.24 no.2
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• pp.197-201
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• 1988

Effects of high concentration of KC1 and caffeine on cytosolic $Ca^{2+}$ level $([Ca^{2+}]_{cyt})$, measured simultaneously with muscle tension using a fluorescent intracellular $Ca^{2+}$ indicator fura 2, were examined in isolated smooth muscle of rat aorta. High $K^+$ (72.7 mM) solution induced sustained increase in both $([Ca^{2+}]_{cyt})$ and tension. In contrast to this, caffeine (20 mM) induced a rapid increase in $([Ca^{2+}]_{cyt})$ followed by a decrease to a level which was higher than the resting level. However, muscle tension showed only a transient increase followed by a decrease below the resting level. In a $Ca^{2+}-free$ solution, high $K^+-induced$ neither $([Ca^{2+}]_{cyt})$ nor tension, whereas caffeine induced a transient increase in both $([Ca^{2+}]_{cyt})$ and muscle tension. These results suggest that high $K^+-induced$ contraction in vascular smooth muscle of rat aorta is due to $Ca^{2+}$ influx whereas caffeine-induced contraction is due to $Ca^{2+}$ release from cellular store. Further, caffeine seems to have an additional effect to decrease the sensitivity of the contractile elements to $Ca^{2+}$.

• YAKHAK HOEJI
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• v.50 no.4
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• pp.293-299
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• 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
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• v.7 no.3
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• pp.221-226
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• 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
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• v.16 no.3
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• pp.249-254
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• 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
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• v.20 no.3
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• pp.352-356
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• 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
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• v.24 no.2
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• pp.281-291
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• 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
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• v.27 no.2
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• pp.191-198
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• 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.

• YAKHAK HOEJI
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• v.58 no.4
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• pp.223-228
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• 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.