• 생약학회지
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• 제16권2호
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• pp.65-72
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• 1985

These studies were conducted to investigate the effect of 'Inchungbaek' water extract on analgesic and sedative actions, the relaxing action of isolated ileums, vasodilating action and blood pressure. The results of these studies were summarized as follows: Analgesic and sedative actions of 'Inchungbaek' were recognized in mice and rats. The relaxing action of isolated ileums were seen in mice and rabbits, antagonist action was seen acetylcholine and $BaCl_2-induced$ contraction of isolated ileums, and then recognized direct action in the ileum smooth muscle. Hypotensive and vasodilating actions due to vascular smooth muscle relaxation were noted in rabbits and cats.

• 동의생리병리학회지
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• 제28권2호
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• pp.169-177
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• 2014

This study aimed to investigate the relaxation effects and its underlying mechanisms of Epimedium koreanum Nakai(EK) in phenylephrine(PE) treated isolated rabbit corpus cavernosum smooth muscle. The dose-dependent relaxation responses of phenylephrine(PE, $1{\times}10^{-6}M$)-precontracted strips to EK at $0.01-3.0mg/m{\ell}$ were measured and also observed after endothelial denudation using organ bath. To analyze the underlying mechanisms of EK-induced relaxation, $N{\omega}$-nitro-L-arginine(L-NNA), methylene blue(MB), tetraethylammonium chloride(TEA), indomethacin(IM) were pretreated before EK extract infused into precontracted strips induced by PE. To investigate cytotoxic activity and nitric oxide(NO) concentration of EK extract on EA.hy926 cells, mitochondrial dehydrogenase activity(MTT) assay and nitric oxide detection kit were used. The cavernous strips were significantly relaxed by EK extract at $0.3mg/m{\ell}$, $1.0mg/m{\ell}$, $3.0mg/m{\ell}$ and the relaxation responses of PE-precontracted strips denuded endothelium also inhibited in comparison with intact endothelium. The pretreatment of L-NNA, MB, TEA reduced EK extract-induced endothelium-dependent relaxation, but the pretreatment of IM didn't affect EK extract-induced endothelium-dependent relaxation. When EK extract was applicated on EA.hy926 cells, the NO concentration was increased. Our findings have shown that EK extract exerts a relaxing effect on corpus cavernosum in part by suppressing influx of extracellular $Ca^{2+}$ through activating the NO-cGMP system.

• 동의생리병리학회지
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• 제30권5호
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• pp.308-313
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• 2016

The purpose of this study is to investigate the effects of Oja-Shingiwhan(OS) in contracted corpus cavernosum smooth muscle and its mechanism. To evaluate the relaxation of OS in contracted corpus cavernosum, OS was treated in strips which were precontracted with phenylephrine(PE). To examine its mechanism, OS was treated into corporal strips contracted by PE after pretreatment of Nω-nitro-L-arginine(L-NNA) and compared with non-pretreatment of _L-NNA. In calcium chloride(Ca²⁺)-free krebs solution, Ca²⁺ 1 mM was treated into corporal strips contracted by PE after pretreatment of OS and compared with non-pretreatment of OS. action were measured by histochemical, immunohistochemical methods. OS significantly affected on the relaxation of corporal strips, and the relaxation effects were inhibited by pretreatment of L-NNA. Contractions induced by Ca²⁺ influx were inhibited by pretreatment of OS in Ca²⁺-free krebs solution. OS increased eNOS positive reaction in corpus cavernosum, but decreased PDE-5 positive reaction. These result suggest that the effect of OS in contracted corpus cavernosum smooth muscle are shown by suppressing extracellular Ca²⁺ influx and increase of eNOS, NO production and decrease of PDE-5.

• Natural Product Sciences
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• 제23권3호
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• pp.169-174
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• 2017

The aim of this study was to investigate the effect and action mechanism of quercetin on penile corpus cavernosum smooth muscle (PCCSM). PCCSM precontracted with phenylephrine (Phe) was treated with four different concentrations of quercetin ($10^{-7}$, $10^{-6}$, $10^{-5}$ and $10^{-4}M$). PCCSM were preincubated with N-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) to block nitric oxide synthase and guanylate cyclase, respectively. The changes in PCCSM tension were recorded, and cyclic nucleotides in the perfusate were measured by radioimmunoassay. The interactions of quercetin with phosphodiesterase type 5 inhibitors (PDE5-Is) such as sildenafil, udenafil and mirodenafil, were also evaluated. PCCSM relaxation induced by quercetin occurred in a concentrationdependent manner. The application of quercetin to PCCSM pre-treated with L-NAME and ODQ significantly inhibited the relaxation. Quercetin significantly increased cGMP in the perfusate. Furthermore, quercetin enhanced PDE5-Is-induced relaxation of PCCSM. Quercetin relaxed the PCCSM by activating the NO-cGMP signaling pathway, and it may be a therapeutic candidate or an alternative treatment for patients with erectile dysfunction who do not completely respond to PDE5-Is.

• 동의생리병리학회지
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• 제18권5호
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• pp.1382-1386
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• 2004

This study was performed for the investigation of vasodilatory efficacy and its underlying mechanisms of Samhwangsasim-tang(SST), herbal remedy. SST relaxed vascular strips precontracted with phenylephrine or KCI(51 mM), but the magnitude of relaxation was greater in phenylephrine(PE) induced contraction. The relaxation effects of SST was endothelium-independent. L-NAME, iNOS inhibitor, and methyl en blue(MB), cGMP inhibitor, did not attenuate the relaxation responses of SST. In the absence of extracellular Ca2+, pre-incubation of the aortic rings with SST significantly reduced the contraction by PE, suggesting that the relaxant action of the SST includes inhibition of Ca/sup 2+/ influx and release of Ca/sup 2+/ from intracellular stores (SR). In addition, the cell death was induced by SST in human aortic smooth muscle cells but not that of human umbilical vein endothelial cells. We conclude that in rat thoracic aorta, SST may induce in part vasodilation through inhibition of Ca/sup 2+/ influx and release of Ca/sup 2+/ from intracellular stores.

• The Korean Journal of Physiology
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• 제29권2호
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• pp.279-289
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• 1995

This study was designed 1) to develop a hypertensive animal model in which the blood pressures (BPs) of symmetric regions (right and left upper extremities) are significantly different and 2) to test the effect of BP per se on the contractility and endothelium-dependent relaxation of vascular smooth muscle. Rabbits were anesthetized with sodium pentobarbital and ventilated with room air via animal respirator. The transverse aorta was exposed through the left second intercostal space and the lumen of the aorta was narrowed partially by ligation using 3-0 silk and a probe at a point between the origins of the brachiocephalic trunk and the left subclavian artery. Four to eight weeks postoperatively, BPs were measured in the carotid artery as the high BP area (proximal to coactation site) and in the femoral artery as the low BP area (distal to coarctation site). In the animal model, pressure-overload hypertension was developed and the BP of the right subclavian artery was higher than that of the left subclavian artery. The concentrations of circulating epinephrine, norepinephrine, angiotensin I, and angiotensin II were measured. The right and left subclavian arteries and their branches were used for isometric tension recording in organ baths and their responsiveness to phenylephrine, serotonin, acetylcholine, and sodium nitroprusside were examined. The BPs of carotid and femoral artery in control animals were $116{\pm} 12/75{\pm}9\;mmHg (mean ${\pm}SEM$) and $130{\pm}16/68{\pm}9\;mmHg$ respectively, while those of carotid and femoral artery in the hypetensive animals were $172{\pm}6/111{\pm}10\;mmHg$ and 136{\pm} 4/100 {\pm}9\;mmHg$ respectively. There were no significant differences in the concentrations of circulating epinephrine, norepinephrine, angiotensin I, and angiotensin II between controls and the animal models. No significant differences were found in the vascular sensitivities to phenylephrine and serotonin between the high pressure-exposed vessels and the low pressure-exposed vessels. However, the endothelium-dependent relaxation to acetylcholine and nitroprusside-induced relaxation showed significant differences between the high pressure-exposed and the low pressure-exposed subclavian arteries. From the above results, we suggest that the contractility of vascular smooth muscle is unchanged by the elevated pressure per se. However, the endothelium-dependent relaxation to acetylcholine and the nitroprusside-induced relaxation are attenuated by pressure.

• The Korean Journal of Physiology
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• 제29권2호
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• pp.233-241
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• 1995

The nonapeptide bradykinin has been shown to exhibit an array of biological activities including relaxation/contraction of various smooth muscles. In order to investigate the effects of bradykinin on the contractility and the electrical activity of antral circular muscle of guinea-pig stomach, the isometric contraction and membrane potential were recorded. Also, using standard patch clamp technique, the $Ca^{2+}-activated$ K currents were recorded to observe the change in cytosolic $Ca^{2+}$ concentration. $0.4 {\mu}M$ bradykinin induced a triphasic contractile response (transient contraction-transient relaxation-sustained contraction) and this response was unaffected by pretreatment with neural blockers (tetrodotoxin, atropine and guanethidine) or with apamin. Bradykinin induced hyperpolarization of resting membrane potential and enhanced the amplitude of slow waves and spike potentials. The enhancement of spike potentials was blocked by neural blockers. Both the bradykinin-induced contractions and changes in membrane potential were reversed by the selective $B_2$-receptor antagonist $(N{\alpha}-adamantaneacetyl-_{D}-Arg-[Hyp, Thy,_{D}-Phe]-bradykinin)$. In whole-cell patch clamp experiment, we held the membrane potential at -20 mV and spontaneous and transient changes of Ca-activated K currents were recorded. Bradykinin induced a large transient outward current, consistent with a calcium-releasing action of bradykinin front the intracellular calcium pool, because such change was blocked by pretreatment with caffeine. Bradykinin-induced contraction was also blocked by pretreatment with caffeine. From these results, it is suggested that bradykinin induces a calciumrelease and contraction through the $B_{2}$ receptor of guinea-pig gastric smooth muscle. Enhancement of slow wave activity is an indirect action of bradykinin through enteric nerve cells embedded in muscle strip.

• The Korean Journal of Physiology
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• 제24권1호
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• pp.77-90
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• 1990

There have been conflicting reports concerning the effect of Panax ginseng on the contractility of vascular smooth muscle, i.e., Panax ginseng extract has been reported to cause relaxation, contraction or to have no effect on the tension of vascular smooth muscle. A further investigation of $Ca^{++}$ stores which supply $Ca^{++}$ for contraction of vascular smooth muscle is needed to understand the underlying mechanisms of this conflicting effect of ginseng alcohol extract (GAE). The present study was intended to examine the sources of calcium mobilized for contraction of vascular smooth muscle by GAE. Aortic ring preparations were made from the rabbit thoracic aorta and endothelial cells were removed from the ring. The contractility of the aortic ring was measured under various experimental conditions and $Ca^{++}$ flux across the membrane of aortic ring and the sarcoplasmic reticulum and mitochondria were measured with a calcium selective electrode. The result were summarized as follows; 1) At low concentration of extracellular $Ca^{++}$, GAE increased the contractility of vascular smooth muscle in dose-dependent fashion except high concentration $Ca^{++}$ (1 mM). 2) In the presence of ryanodine, GAE still increased contractility of vascular smooth muscle as much as control group, but in the presence of caffeine, GAE increased it significantly. i.e. Their effects seemed to be additive. 3) In the presence of verapamil+lanthanum, and verapamil+lanthanum+ryanodine, the contractility of the vascular smooth muscle was decreased, but a dose dependent increase in vascular tension was still demonstrated by GAE although total tension was low. 4) GAE increased $Ca^{++}$ efflux from vascular smooth muscle cells, but have no effect on $Ca^{++}$ influx. 5) GAE increased $Ca^{++}$ efflux from sarcoplasmic reticulum and mitochondria vesicles. From the above results, it may be concluded that GAE increased the release of $Ca^{++}$ from sarcoplasmic reticulum, mitochondria or other intracellular $Ca^{++}$ stores of vascular smooth muscle, but it does not increase $Ca^{++}$ influx across the plasma membrane.

• 동의생리병리학회지
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• 제16권5호
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• pp.1060-1065
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• 2002

LC20 phosphorylation and PKC α play an important role in modulation of contractile activity of smooth muscle. Besides, myosin phosphatase is also related with smooth muscle contraction in signaling pathways. We previously demonstrated that Crataegi Fructus inhibited phenylephrine-induced contraction and which might be implicated in nitrite formation(Son et al., 2002). In this study, we investigated the effects of butanol fraction of Crataegi Fructus(BFFC) on the localization of α-protein kinease C(PKC α) and myosin phosphatase subnits(MPs) in freshly isolated single ferret potal vein cells, and phosphorylation of LC20 during phenylephrine stimulation. In PKC α and MPs localization, BFFC blocked its translocation from the cytosol to the cell membrane by treatment of phenylephrine. BFFC have also dephosphorylated LC20 phosphorylation by phenylephrine stimulation under basal level, but no significant. These results indicate that the relaxation effect of BFFC is associated with inhibition of PKC α activation and MPs dissociation, and thus myosin phosphatase activity may be increased.

• The Korean Journal of Physiology
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• 제28권2호
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• pp.181-190
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• 1994

Endothelium-derived relaxing factor (EDRF) activates guanylate cyclase which mediates the formation of cGMP from GTP in vascular smooth muscle. It is well known that endothelium-dependent relaxation is impaired in spontaneously hypertensive rats (SHR). However, it is still unknown whether the impaired endothelium-dependent relaxation in SHR results from the reduced release of EDRF or from the decrease of vascular response to EDRF. We investigated the effects of cGMP on the contractility and Ca movement in the aorta of SHR and Wistar-Kyoto rats (WKY). The amplitude of the endothelium-dependent relaxation to actylcholine (ACh) was significantly less in SHR than in WKY. L-arginine $(10^{-3}M)$ did not increase endothelium-dependent relaxation in both strains. Sodium nitroprusside (SNP), an activator of guanylate cyclase, relaxed the 40 mM $K^+-induced$ contraction in a dose-dependent manner $(10^{-10}{\sim}10^{-6}\;M)$ in the endothelium-rubbed aortic strips of both strains. However, there was no significant difference in these relaxations between WKY and SHR. 8-bromo-cyclic guanosine monophosphate (8-Br-cGMP), a cell membrane-permeable derivative of cGMP relaxed the 40 mM $K^+-induced$ contraction in a dose-dependent manner $(10^{-6}{\sim}10^{-4}\;M)$ in the endothelium-rubbed aortic strips of both strains. Also norepinephrine $(10^{-6}\;M)-induced$ contractions in normal and Ca-free Tyrode's solution were suppressed by the pretreatment with 8-Br-cGMP $(10^{-4}\;M)$ in either strain. However, the amplitudes of suppression induced by 8-Br-cGMP were greater in SHR than that in WKY. Basal $^{45}Ca$ uptake and 40mM $K^+-stimulated\;^{45}Ca$ uptake were not suppressed by pretreatment with 8-Br-cGMP $(10^{-4}\;M)$ in single aortic smooth muscle cells of both SHR and WKY. From the above results, it is suggested that cGMP decreases Ca sensitivity in vascular smooth muscle cells and that the impaired endothelium-dependent relaxation in the aortic strips of SHR is not the result of a reduced vascular response to EDRF.