• The Journal of Korean Medicine
• /
• v.19 no.2
• /
• pp.228-243
• /
• 1998

This study was undertaken to evaluate the effect of Sunghyangchungisan (SHCS) on the regulation of vascular tone. Vascular rings isolated from rabbit carotid artery were myographed isometrically in isolated organ baths and the effect of SHCS on contractile activities were determined. SHCS relaxed the arterial rings which were pre-contracted by phenylephrine(PE). The responses to SHCS were partially dose-dependent at concentrations lower than 0.5 mg/ml. When SHCS was applied prior to the exposure to PE, it inhibited the PE-induced contraction by a similar magnitude which was comparable to the relaxation of pre-contracted arterial rings. Washout of SHCS after observing its relaxant effect resulted in a full recovery of PE-induced contractions, indicating that the action mechanism is reversible. The observation that SHCS did not change the $ED_{50}$ of PE on its dose-response curve ruled out the possible interaction of SHCS and ${\alpha}-receptor$. The relaxant effect of SHCS was not affected by removal of endothelium, and pretreatment of the arterial rings with methylene blue or nitro-L-arginine. This results suggest that the action of SHCS is not mediated by endothelium nor soluble guanylate cyclase. SHCS relaxed high $K^{+}-induced$ contractions as well, whereas it failed to relax phorbol ester-induced contractions. When contraction was induced by additive application of $Ca^{2+}$ in arterial rings which were pre-depolarized by high $K^+$ in a $Ca^{2+}-free$ solution, the relaxant effect of SHCS was attenuated by increasing the $Ca^{2+}$ concentration. SHCS, when applied to the arterial rings pre-contracted by PE and then relaxed by nifedipine, a $Ca^{2+}$ channel blocker, did not show additive relaxation. From above results, it is suggested that SHCS relax PE-induced contraction of rabbit carotid artery in an endothelium-independent manner, and inhibition of $Ca^{2+}$ influx may contribute to the underling mechanism.

• The Korean Journal of Physiology and Pharmacology
• /
• v.19 no.3
• /
• pp.257-262
• /
• 2015

It is well known that cigarette smoke can cause erectile dysfunction by affecting the penile vascular system. However, the exact effects of nicotine on the corpus cavernosum remains poorly understood. Nicotine has been reported to cause relaxation of the corpus cavernosum; it has also been reported to cause both contraction and relaxation. Therefore, high concentrations of nicotine were studied in strips from the rabbit corpus cavernosum to better understand its effects. The proximal penile corpus cavernosal strips from male rabbits weighing approximately 4 kg were used in organ bath studies. Nicotine in high concentrations ($10^{-5}{\sim}10^{-4}M$) produced dose-dependent contractions of the corpus cavernosal strips. The incubation with $10^{-5}M$ hexamethonium (nicotinic receptor antagonist) significantly inhibited the magnitude of the nicotine associated contractions. The nicotine-induced contractions were not only significantly inhibited by pretreatment with $10^{-5}M$ indomethacin (nonspecific cyclooxygenase inhibitor) and with $10^{-6}M$ NS-398 (selective cyclooxygenase inhibitor), but also with $10^{-6}M$ Y-27632 (Rho kinase inhibitor). Ozagrel (thromboxane $A_2$ synthase inhibitor) and SQ-29548 (highly selective TP receptor antagonist) pretreatments significantly reduced the nicotine-induced contractile amplitude of the strips. High concentrations of nicotine caused contraction of isolated rabbit corpus cavernosal strips. This contraction appeared to be mediated by activation of nicotinic receptors. Rho-kinase and cyclooxygenase pathways, especially cyclooxygenase-2 and thromboxane $A_2$, might play a pivotal role in the mechanism associated with nicotine-induced contraction of the rabbit corpus cavernosum.

• The Korean Journal of Physiology and Pharmacology
• /
• v.15 no.3
• /
• pp.143-147
• /
• 2011

Defensins, cysteine-rich cationic polypeptides released from neutrophils, are known to have powerful antimicrobial properties. In this study, we sacrificed 30 rats to investigate the effects of ${\alpha}$-defensin 1 on detrusor muscle contractions in isolated rat bladder. From the experiments we found relaxing effects of ${\alpha}$-defensin 1 on the contractions induced by phenylephrine (PE) but not by bethanechol (BCh) in the detrusor smooth muscles. To determine the mechanisms of the effects of ${\alpha}$-defensin 1, the changes of effects on PE-induced contraction by ${\alpha}$-defensin 1 pretreatment were observed after pretreatment of Rho kinase inhibitor (Y-27632), protein kinase C (PKC) inhibitor (Calphostin C), potent activator of PKC (PDBu; phorbol 12,13-dibutyrate), and NF-${\kappa}B$ inhibitors (PDTC; pyrrolidinedithiocarbamate and sulfasalazine). The contractile responses of PE ($10^{-9}{\sim}10^{-4}$ M) were significantly decreased in some concentrations of ${\alpha}$-defensin 1 ($5{\times}10^{-9}$ and $5{\times}10^{-8}$ M). When strips were pretreated with NF-kB inhibitors (PDTC and sulfasalazine; $10^{-7}{\sim}10^{-6}$ M), the relaxing responses by ${\alpha}$-defensin 1 pretreatment were disappeared. The present study demonstrated that ${\alpha}$-defensin 1 has relaxing effects on the contractions of rat detrusor muscles, through NF-${\kappa}B$ pathway. Further studies in vivo are required to clarify whether ${\alpha}$-defensin 1 might be clinically related with bladder dysfunction by inflammation process.

• The Korean Journal of Physiology and Pharmacology
• /
• v.21 no.6
• /
• pp.617-623
• /
• 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.

• Archives of Pharmacal Research
• /
• v.29 no.1
• /
• pp.34-39
• /
• 2006

The antispasmodic and vasodilator activities of a newly synthesized piperidine derivative (1-(4'fluorophenacyl)-4-hydroxy-4-phenyl-piperidinium chloride) were studied in vitro. The test compound exhibited a dose-dependent relaxant effect on the spontaneous and $K^+$ (75 mM)-induced contractions of isolated rabbit jejunum with respective $EC_{50}$ values of 0.01 mM(0.01-0.02, 95% CI) and 0.30 mM (0.17-0.56). The $Ca^{++}$ channel blocking (CCB) activity was confirmed when the test compound (0.1-0.2 mM) shifted the $Ca^{++}$ dose-response curves to the right, similar to that produced by verapamil ($0.1-1.0{\mu}M$), a standard CCB. In the isolated rabbit aorta, the test compound showed a dose-dependent vasodilator effect on $K^+$ (75 mM)-induced contractions with an $EC_{50}$ value of 0.08 mM (0.02-0.26) while also suppressed the norepinephrine ($1{\mu}M$) control peak responses with $EC_{50}$ value of 0.08 mM (0.05-0.13, n=5). When tested in Langendorff perfused rabbit heart preparation, the test compound exhibited a negligible inhibitory effect on the rate or force of atrial and ventricular contractions when tested up to 5 mM. The results show smooth muscle-selective relaxant effect of the test compound on intestinal and vascular preparations mediated possibly via blockade of voltage and receptor-operated $Ca^{++}$ channels.

• PNF and Movement
• /
• v.17 no.3
• /
• pp.487-497
• /
• 2019

Purpose: This tutorial review investigated the effect of prior fatigue and passive stretches on eccentric contraction-induced muscle injuries, as well as the underlying mechanisms of eccentric contraction-related injuries. Methods: Contraction-induced muscle damage is the most common disabling problem in sports and routines. The mechanisms underlying the pathology and prevention of muscle damage lessened by prior fatigue or stretches are critical in assessing musculoskeletal injuries. Even though there are treatments to reduce eccentric contraction-induced muscle injuries, fatigue negatively influences them. Therefore, we reviewed previous studies on eccentric contraction-induced muscle injuries with prior treatments using the MEDLINE and PubMed databases. Results: Prior passive stretching had a preventative and therapeutic effect, but prior lengthening contractions did not. On the other hand, prior isometric contractions involving relatively small forces may not provide a sufficient stimulus to induce protection. As a result, high force isometric contractions may be necessary. The studies supported the positive effects of prior fatigue, concluding that it was a factor in determining the amount of damage caused by eccentric exercise. This was due to a reduction in force and increased temperature. Studies that did not support the positive effects of prior fatigue concluded that a shift in optimal length to a longer length and reduced energy absorption during lengthening are evidence that fatigue is not related to muscle injuries induced by lengthening. Conclusion: The variability of the experiment models, conditions, muscles, and treatment methods make it necessary to interpret the conditions of previous studies carefully and draw conclusions without making direct comparisons. Thus, additional studies should be carefully conducted to investigate the positive effect of fatigue on lengthening.

• The Journal of Korean Obstetrics and Gynecology
• /
• v.29 no.4
• /
• pp.24-33
• /
• 2016

Objectives: The aim of this study was to demonstrate the benefit of Traditional Korean Medicine as an adjuvant therapy in management of early uterine contractions and the prevention of Preterm Birth (PTB). Methods: It is a case report of a 38 year-old-woman hospitalized for irregular uterine contractions and cervical change at 33^+3/7weeks of gestation. After 7 trials of IVF and artificial insemination, conception was successful via IVF with help of traditional Korean medicines. 2 TKMs were prescribed: Gami-danggui-san, and Antae-eum. 120 ml of Gami-danggui-san was given twice a day morning and evening along with same amount of Antae-eum once a day from 31 August 2013 to 28 November 2013. Tocolytics (Ritodrine) was administered as a first aid for maintenance of pregnancy. Information regarding progress until the delivery was collected during the patient’s visit. Results: As of 34^+2/7 weeks of gestation, intermittent uterine contractions appeared (5-12 min) on cardiotocography and vaginal bleeding was also smeared at 34^+3/7 weeks. However, enhanced tocolytics and continuous administration of herbal medicine sustained the pregnancy to term. At 37^+2/7 weeks, no sign of labor with restored cervical length was confirmed. The woman gave a term birth to a healthy infant via vaginal delivery at 39^+3/7 gestational weeks. Conclusions: Our report implies the potential of herbal medicine as a adjuvant therapy for preterm labor treatment. Further studies are needed to assess the safety and efficacy of TKM herbal medicine as a therapeutic alternative for curing preterm birth.

• The Korean Journal of Physiology and Pharmacology
• /
• v.2 no.3
• /
• pp.361-368
• /
• 1998

The spontaneous contractions of gastric smooth muscles are regulated by slow waves, which are modulated by both nervous system and humoral agents. This study was designed to examine the effects of prostaglandin $E_2$ ($PGE_2$) on the contractile and electrical activities of antral smooth muscles in guinea-pig stomach, using an intracellular recording technique. To elucidate the underlying mechanism for its effect on contractility, ionic currents were also measured using a whole-cell patch clamp method. The basal tone by $PGE_2$ was variable, whereas the magnitude of phasic contractions was reduced ($19.0{\pm}2.1%$, n=19). The resting membrane potentials were hyperpolarized ($-4.4{\pm}0.5%$ mV, n=10), and plateau potentials were lowered ($-2.9{\pm}0.5%$ mV, n=10). In most cases, however, the initial peak potentials of slow waves were depolarized more by $PGE_2$ than those of control. The frequency of the slows wave was increased from $5.7{\pm}0.2$ cycles/min to $6.5{\pm}0.2$ (n=22). Voltage-operated $Ca^{2+}$ currents were decreased by $PGE_2$ (n=5). Voltage-operated $K^+$ currents, both Ca-dependent and Ca-independent, were increased (n=5). These results suggest that $PGE_2$ plays an important role in the modulation of gastric smooth muscle activities, and its inhibitory effects on the contractility and activities of slow waves are resulted from both decrease of $Ca^{2+}$ currents and increase of $K^+$ currents.

• The Korean Journal of Physiology and Pharmacology
• /
• v.2 no.6
• /
• pp.695-703
• /
• 1998

$[K^+]_o$ can be increased under a variety of conditions including subarachnoid hemorrhage. The increase of $[K^+]_o$ in the range of $5{\sim}15$ mM may affect tensions of blood vessels and can change their sensitivity to various vasoactive substances. Therefore, it was examined in the present study whether the sensitivity of cerebral arteries to vasoactive substances can be changed with the moderate increase of $[K^+]_o$, using Mulvany-type myograph and $[Ca^{2+}]_c$ measurement. The contractions of basilar artery and branch of middle cerebral artery induced by histamine were not increased with the elevation of $[K^+]_o$ from 6 mM to 9 mM or 12 mM. On the contrary, the contractions induced by serotonin were significantly increased with the elevation of $[K^+]_o$. The contractions were also significantly increased by the treatment with nitro-L-arginine $(10^{-4}$ M for 20 minutes). In the nitro-L-arginine treated arteries, the contractions induced by serotonin were significantly increased with the elevation of $[K^+]_o$ from 6 mM to 12 mM. $K^+-induced$ relaxation was evoked with the stepwise increment of extracellular $K^+$ from 0 or 2 mM to 12 mM by 2 mM in basilar arterial rings, which were contracted by histamine. But $[K^+]_o$ elevation from 4 or 6 mM to 12 mM by the stepwise increment evoked no significant relaxation. Basal tension of basilar artery was increased with $[K^+]_o$ elevation from 6 mM to 12 mM by 2 mM steps or by the treatment with ouabain and the increase of basal tension was blocked by verapamil. The cytosolic free $Ca^{2+}$ level was not increased by the single treatment with serotonin or with the elevation of $[K^+]_o$ from 4 mM to 8 or 12 mM. In contrast to the single treatment, the $Ca^{2+}$ level was increased by the combined treatment with serotonin and the elevation of $[K^+]_o$. The increase of free $Ca^{2+}$ concentration was blocked by the treatment with verapamil. These data suggest that the sensitivity of cerebral artery to serotonin is increased with the moderate increase of $[K^+]_o$ and the increased sensitivity to serotonin is due to the increased $[Ca^{2+}]_i$ induced by extracellular $Ca^{2+}$ influx.

• The Korean Journal of Physiology
• /
• v.28 no.2
• /
• pp.169-179
• /
• 1994

The effect of extracellular and intracellular pH on vascular tone and $^{45}Ca$ uptake were investigated in aortic strips and dispersed single aortic smooth muscle cells of spontaneously hypertensive rats (SHR) and aged-matched Wistar-Kyoto rats (WKY). The contraction produced by a change of extracellular pH (pHo) in the range of $6.5{\sim}8.3$ was estimated by comparison with the level of vascular tone at pH 7.4. Contraction was induced below pHo 6.5 in WKY, pHo 7.1 in SHR, and over pHo 8.0 on both strains. The amplitude of contraction induced by high pHo (over pHo 7.7) was similar in SHR and WKY, but that induced by low pHo (below pHo 7.1) in SHR was greater than that in WKY. Either high pHo- or low pHo-induced contractions in WKY and SHR were not induced in the Ca-free Tyrode's solution and were induced by the addition of Ca. $^{45}Ca$ uptake increased progressively as pHo was increased from 6.8 to 8.1 in the single aortic smooth muscle cells of WKY and SHR. $NH_4Cl$ induced a gradually developing contraction in a dose-dependent manner $(5\;mM{\sim}30\;mM)$ and the removal of $NH_4Cl$ induced transient contraction was followed by profound relaxation in the aortic rings of both strains. The contractions induced by $NH_4Cl$ or by the removal of $NH_4Cl$ in SHR were significantly greater than that in WKY. These contractions were not induced in Ca-free Tyrode's solution. $^{45}Ca$ uptake was increased by $NH_4Cl$ (20 mM) and was not changed by the removal of $NH_4Cl$ (20 mM) in the aortic strips of WKY and SHR. As a summary of above results, the vascular tone of SHR was more sensitive to the change pHi and pHo than that of WKY. The contractions induced by change of extracellular or intracellular pH depended on extracellular Ca in the aorta of SHR nnd WKY. However, the Ca uptake was in accord with the changes of contraction but increase in contraction by low pH was not accompanied by an increase in Ca uptake in both strains.