• The Korean Journal of Physiology
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• v.24 no.2
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• pp.293-303
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• 1990

The contractile action of barium $(Ba^{2+})$ was investigated in the arterial strip of rabbit renal artery. The helical strip of isolated renal artery was immersed in the Tris-buffered Tyrode's solution equilibrated with 100% $O_2$ at $37^{\circ}C$ and its isometric tension was measured. $Ba^{2+}-induced$ contraction of arterial strip was dose-dependent and its maximal tension corresponded to $92.1{\pm}4.5%$ of tension by $K^+(100\;mM)$. $Ba^{2+}-induced$ contraction did not show the tachyphylactic phenomenon in the normal Tyrode's solution. $Ba^{2+}$ induced the tonic contraction in the $Ca^{2+}-free$ tyrode's solution and that was increased by the extracellula addition of $Ca^{2+}$. During the repeated exposure of the same dose of $Ba^{2+}\;(10\;mM)$ in the $Ca^{2+}-free$ Tyrode's solution, $Ba^{2+}-induced$ contraction was progressively decreased. Even though the intracellular NE-and caffeine-sensitive $Ca^{2+}$ was depleted, $Ba^{2+}$ induced the tonic contraction. After the pretreatment of lanthnum or verapamil, $Ba^{2+}$ did not induce contraction. $Ba^{2+}-induced$contraction was suppressed by extracellular $K^+$ in the normal Tyrode's solution and that was dependent on $K^+$ concentration. Suppressive effect of $K^+\;(14\;mM)$ on the $Ba^{2+}-induced$ contraction was also dependent on the intracellular $Ca^{2+}$ concentration. From the above resuts, it is suggested that $Ba^{2+}$ activate indirectly the contractile process by promoting the mobilization of intracellular $Ca^{2+}$ and the influx of extracellular $Ca^{2+}$. It is also suggested that action of $Ba^{2+}$ on the $Ca^{2+}-activated$ $K^+$ channel can result in the depolarization of cell membrane in the rabbit renal artery.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.4
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• pp.385-395
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• 2017

Vasoconstrictive properties of sympathomimetic drugs are the basis of their widespread use as decongestants and possible source of adverse responses. Insufficiently substantiated practice of combining decongestants in some marketed preparations, such are those containing phenylephrine and lerimazoline, may affect the overall contractile activity, and thus their therapeutic utility. This study aimed to examine the interaction between lerimazoline and phenylephrine in isolated rat aortic rings, and also to assess the substrate of the obtained lerimazoline-induced attenuation of phenylephrine contraction. Namely, while lower concentrations of lerimazoline ($10^{-6}M$ and especially $10^{-7}M$) expectedly tended to potentiate the phenylephrine-induced contractions, lerimazoline in higher concentrations ($10^{-4}M$ and above) unexpectedly and profoundly depleted the phenylephrine concentration-response curve. Suppression of NO with NO synthase (NOS) inhibitor $N^w$-nitro-L-arginine methyl ester (L-NAME; $10^{-4}M$) or NO scavanger $OHB_{12}$ ($10^{-3}M$), as well as non-specific inhibition of $K^+$-channels with tetraethylammonium (TEA; $10^{-3}M$), have reversed lerimazoline-induced relaxation of phenylephrine contractions, while cyclooxygenase inhibitor indomethacin ($10^{-5}M$) did not affect the interaction between two vasoconstrictors. At the receptor level, non-selective 5-HT receptor antagonist methiothepin reversed the attenuating effect of lerimazoline on phenylephrine contraction when applied at $3{\times}10^{-7}$ and $10^{-6}M$, but not at the highest concentration ($10^{-4}M$). Neither the 5-$HT_{1D}$-receptor selective antagonist BRL 15572 ($10^{-6}M$) nor 5-$HT_7$ receptor selective antagonist SB 269970 ($10^{-6}M$) affected the lerimazoline-induced attenuation of phenylephrine activity. The mechanism of lerimazoline-induced suppression of phenylephrine contractions may involve potentiation of activity of NO and $K^+$-channels and activation of some methiothepin-sensitive receptors, possibly of the 5-$HT_{2B}$ subtype.

• YAKHAK HOEJI
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• v.43 no.2
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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 Pharmacology
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• v.26 no.2
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• pp.121-126
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• 1990

The contractility of isolated rat atria, suspended in Krebs-Ringer bicarbonate medium containing 5.5mM glucose, was depressed approximately 50% by 0.1 mM of lidocaine. Partial recovery of the lidocaine-depressed contractility was achieved by the metabolizable substrates pyruvate, acetate, and fructose, but not by addition of glucose. Glucose produced the dose-dependent increase in the force of contraction of normal atria, whereas pyruvate, acetate, and fructose produced no significant effect in the contractile activity of the normal atria. In the absence of exogenous glucose lidocaine produced more marked depression of atrial contractility than that in the presence of exogenous glucose. The results of this study may confirm that the utilization of cardiac glycogen is also inhibited by lidocaine at sites of the glucose phosphate isomerase step or step between glycogen to glucose-6-phosphate.

• Transactions of the Korean Society of Mechanical Engineers B
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• v.38 no.8
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• pp.715-720
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• 2014

In order to maximize the effect of left ventricular assist device (LVAD) on ventricular unloading, the therapy should be begun at appropriate level of heart failure severity. We predicted pumping efficacy of LVAD according to the severity of heart failure theoretically. We used 3 dimensional finite element model of ventricle coupled with 6 Wind-kessel compartmental model of vascular system. Using the computational model, we predicted cardiac responses such as contractile ATP consumption of ventricle, left ventricular pressure, cardiac output, ejection fraction, and stroke work according to the severity of ventricular systolic dysfunction under the treatments of continuous LVAD. Contractile ATP consumption, which indicates the ventricular energetic loading condition decreased maximally at the $5^{th}$ level heart-failure under LVAD therapy. We conclude that optimal timing for LVAD treatment is $5^{th}$ level heart-failure when considering LVAD treatment as "bridge to recovery".

• Korean Journal of Animal Reproduction
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• v.18 no.2
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• pp.101-104
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• 1994

The purpose of the present study was to examine the in vivo activity of oxytocin antagonist I (AI)in the nonpregnant estrous rat. Cannulas were placed in the jugular vein for infusing compounds and a water-filled balloon-tipped cannula placed in one uterine horn for assessing uterine activity. Uterine contractions were monitored with a Grass Polygraph and contractile activity determined as the integrated area for 10 minutes. Five minutes after infusing 5 ${\mu}\textrm{g}$ of AI, 100mU of oxytocin was given as an in bolus injection and repeated every hour for 5 hours. At five minutes, 1 and 2 hours after injection AI the uterine contractile response to 100 mU of oxytocin was significantly inhibited compared to controls(p<0.05). At 3, 4 and 5 hours no differences in response were detected compared to controls(p>0.05). These results in conjunction with other reports from our laboratory suggest that AI has the potential of being a potent and specific tocolytic for prevention of preterm labor in humans.

• Proceedings of the SCSK Conference
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• 2003.09a
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• pp.192-202
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• 2003

The wrinkles correspond to the most obvious expression of skin ageing and are manifested by changes on the organization and dermal structure. In the extracellular matrix, decreased quantities of collagens and glycosaminoglycans as well as a deterioration of the fibrillary network is noted, result in a reduction of dermal thickness. In addition, the activity of the collagenases increases in contrast to the synthesis of collagen fibers. Nor are cells spared during the aging process. We thus studied and compared the contractile capacity as well as the synthesis capacity of normal human fibroblasts and human fibroblasts obtained from biopsies of forehead wrinkles. The capacity of the fibroblasts to be adhered to the collagen network and to maintain a three-dimensional structure of dermis was studied on a model of equivalent dermis. The metabolic activity was studied by evaluating the capacities of synthesis of collagen I, main component of dermis. Human fibroblasts resulting from the forehead wrinkle contract less the gel of collagen than the normal human fibroblasts and present an activity of biosynthesis of collagen I less important than normal human fibroblasts. These results show that fibroblasts with aging present a deceleration of their metabolic activity and lose their capacity of adhesion to collagen fibers thus limiting the possibility of organizing the dermal tissue. We investigated the potential of an active ingredient able to compensate for the reduction of the metabolic activity and to restore the contractile capacity of fibroblasts obtained from forehead wrinkles. This effect was compared with a reference molecule: the vitamin C.

• The Journal of Internal Korean Medicine
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• v.1 no.1
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• pp.25-34
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• 1976

The extract of commercial mistletoe caused transient contraction of mouse ileum in vitro at the level of $7{\times}10^{-4}g/ml$ and augmented significantly its peristalsis. When the ileum was pre-treated With $10^{-6}g/ml$ of adrenaline the administration of the extract at a level of $10^{-4}g/ml$ blocked the contraction. The increase inperistalsis and intention was also observed in rabbit ileum in vitro with the administration of the extract at a level of $10^{-1}g/ml$ but these phenomenon were inhibited by the adrenaline treatment at a level of $10^{-6}g/ml.$ When the extract was applied to spirally cut strips of thoracic aorta at the level of $10^{-3}g/ml$ the contractile action of adrenaline was significantly inhibited. When the extract was infused to auricular blood vessel of rabbit at the rate of $10^{-4}g/ml,\;10^{-3}g/ml,\;10^{-2}g/ml$ and $10^{-1}g/ml$ increases in number of drops by 70%, 77%, 93% and 100% were observed if the maximum number of drops caused by $10^{-1}g/ml$ is considered to be 100%. The duration of prolongation was proportionate to the increase in concentration of the extract. Hypotensive action of the extract and its duration were proportionately increased as the quantity of the extract increased. The increase in number and depth of respiration observed during the hypotensive status was brought to the normal when the tension became normal. In view of these observations it is concluded that the extract of commercial mistletoe has a contractile action of acetylcholine effect in the ileum of mouse and rabbit, loosens both aorta and smooth muscle and promotes peripheral circulation. As for the hypotensive action it is concluded that the action is brought about by the decrease in peripheral circulatory resistance due to the antagonism between acetylcholine and adrenaline.

• Natural Product Sciences
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• v.5 no.1
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• pp.25-32
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• 1999

The pharmacological actions of ambrein were investigated alone or in combination as a pretreatment with agonists (adrenaline, noradrenaline, acetylcholine, histamine, nicotine), antagonists (atropine, atenolol) and calcium channel blocker (verapamil) in vivo in anaesthetized SWR rats using blood pressure, heart rate and myocardial contractility as parameters. Ambrein in the dose range of 50-200 mg/kg to the normotensive anaesthetized rats demonstrated negative chronotropic effect and increased the myocardial contractility significantly. At the mid dose (100 mg/kg) this increase in contractile force was 36% and 44% above the normal at 30 min and 60 min intervals post-treatment, respectively. Both of the lower and high doses (50 mg/kg and 200 mg/kg) had similar effects. Furthermore, this contractile response was dose related. Also, this compound produced a considerable increase in myocardial contractility when used as a pretreatment with some agonists and antagonists. The results on blood pressure did not show a considerable change when ambrein was used alone. However, ambrein pretreatment at the dose of 100 mg/kg did not block the effects of adrenaline, noradrenaline, isoprenaline and acetylcholine on heart rate and blood pressure. On the other hand, this pretreatment attenuated the sympathoadrenal effects of nicotine significantly. Chronotropic and blood pressure changes produced by histamine were also inhibited by ambrein pretreatment. This pretreatment significantly reversed the effects of atenolol but failed to demonstrate any change in the negative chronotropic, inotropic and hypotensive responses induced by verapamil. It is concluded that ambrein induced nonselective dose dependent antagonism of the effects of some agonists and antagonists require contribution of some neuromediators. However, the positive isotropic effects of ambrein possibly involve the enhancement of slow Ca channels and/or activation of ${\beta}-adrenergic$ receptors in the heart. At this moment it is difficult to explain the exact mode of action of ambrein and the studies dealing with Ca channel blocker and adrenergic blocker followed by ambrein may help to define the factors which contribute to its positive inotropic effects.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.2
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• pp.113-120
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• 2000

To investigate the mechanism of smooth muscle contraction induced by emptying of intracellular $Ca^{2+}$ stores, we measured isometric contraction and $^{45}Ca^{2+}$ influx. $CaCl_2$ increased $Ca^{2+}$ store emptying- induced contraction in dose-dependent manner, but phospholipase C activity was not affected by the $Ca^{2+}$ store emptying-induced contraction. The contraction was inhibited by voltage-dependent $Ca^{2+}$ channel antagonists dose dependently, but not by TMB-8 (intracellular $Ca^{2+}$ release blocker). Both PKC inhibitors (H-7 and staurosporine) and tyrosine kinase inhibitors (genistein and methyl 2,5-dihydroxycinnamic acid) significantly inhibited the contraction, but calmodulin antagonists (W-7 and trifluoperazine) had no inhibitory effect on the contraction. The combined inhibitory effects of protein kinase inhibitors, H-7 and genistein, together with verapamil were greater than that of each one alone. In $Ca^{2+}$ store-emptied condition, $^{45}Ca^{2+}$ influx was significantly inhibited by verapamil, H-7 or genistein but not by trifluoperazine. However combined inhibitory effects of protein kinase inhibitors, H-7 and genistein, together with verapamil were not observed. Therefore, this kinase pathway may modulate the sensitivity of contractile protein. These results suggest that contraction induced by emptying of intracellular $Ca^{2+}$ stores was mediated by influx of extracellular $Ca^{2+}$ through voltage-dependent $Ca^{2+}$ channel, also protein kinase C and/or tyrosine kinase pathway modulates the $Ca^{2+}$ sensitivity of contractile protein.