• Title/Summary/Keyword: arterial relaxation

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Diverse Mechanisms of Relaxin's Action in the Regulation of Smooth Muscles and Extracellular Matrix of Vasculature and Fibrosis (혈관과 섬유증의 평활근 및 세포외기질 조절에 대한 릴랙신의 다양한 작용기전)

  • Min, Gyesik
    • Journal of Life Science
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    • v.32 no.2
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    • pp.175-188
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    • 2022
  • Relaxin has been demonstrated to have regulatory functions on both the smooth muscle and extracellular matrix (ECM) of blood vessels and fibrotic organs. The diverse mechanisms by which relaxin acts on small resistance arteries and fibrotic organs, including the bladder, are reviewed here. Relaxin induces vasodilation by inhibiting the contractility of vascular smooth muscles and by increasing the passive compliance of vessel walls through the reduction of ECM components, such as collagen. The primary cellular mechanism whereby relaxin induces arterial vasodilation is mediated by the endothelium-dependent production of nitric oxide (NO) through the activation of RXFP1/PI3K, Akt phosphorylation, and eNOS. In addition, relaxin triggers different alternative pathways to enhance the vasodilation of renal and mesenteric arteries. In small renal arteries, relaxin stimulates the activation of the endothelial MMPs and EtB receptors and the production of VEGF and PlGF to inhibit myogenic contractility and collagen deposition, thereby bringing about vasodilation. Conversely, in small mesenteric arteries, relaxin augments bradykinin (BK)-evoked relaxation in a time-dependent manner. Whereas the rapid enhancement of the BK-mediated relaxation is dependent on IKCa channels and subsequent EDH induction, the sustained relaxation due to BK depends on COX activation and PGI2. The anti-fibrotic effects of relaxin are mediated by inhibiting the invasion of inflammatory immune cells, the endothelial-to-mesenchymal transition (EndMT), and the differentiation and activation of myofibroblasts. Relaxin also activates the NOS/NO/cGMP/PKG-1 pathways in myofibroblasts to suppress the TGF-β1-induced activation of ERK1/2 and Smad2/3 signaling and deposition of ECM collagen.

Effect of Epidural Block under General Anesthesia on Pulse Transit Time (전신마취시 경막외 차단술 병용이 맥파전달시간에 미치는 영향)

  • Choi, Byeong-Cheol;Kim, Seong-Min;Jung, Dong-Keun;Kim, Gi-Ryon;Lee, He-Jeong;Jeon, Gey-Rock
    • Journal of the Korean Society for Nondestructive Testing
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    • v.25 no.4
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    • pp.262-267
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    • 2005
  • Epidural block under general anesthesia has been widely used to control postoperative pain. In this anesthetic state many hemodynamic parameters are changed. Moreover pulse transit time is influenced by this memodynamic change. m change in the finger and the toe due to relaxation of arterial wall muscle after general anesthesia and epidural block under general anesthesia. This study, in the both general anesthesia and epidural block under general anesthesia, ${\Delta}PTT$ of the toe and of the finger are measured. In addition, ${\Delta}PTT$(toe-finger) of the epidural block under general anesthesia and of the general anesthesia were compared.

Canonical Transient Receptor Potential Channels and Their Link with Cardio/Cerebro-Vascular Diseases

  • Xiao, Xiong;Liu, Hui-Xia;Shen, Kuo;Cao, Wei;Li, Xiao-Qiang
    • Biomolecules & Therapeutics
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    • v.25 no.5
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    • pp.471-481
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    • 2017
  • The canonical transient receptor potential channels (TRPCs) constitute a series of nonselective cation channels with variable degrees of $Ca^{2+}$ selectivity. TRPCs consist of seven mammalian members, TRPC1, TRPC2, TRPC3, TRPC4, TRPC5, TRPC6, and TRPC7, which are further divided into four subtypes, TRPC1, TRPC2, TRPC4/5, and TRPC3/6/7. These channels take charge of various essential cell functions such as contraction, relaxation, proliferation, and dysfunction. This review, organized into seven main sections, will provide an overview of current knowledge about the underlying pathogenesis of TRPCs in cardio/cerebro-vascular diseases, including hypertension, pulmonary arterial hypertension, cardiac hypertrophy, atherosclerosis, arrhythmia, and cerebrovascular ischemia reperfusion injury. Collectively, TRPCs could become a group of drug targets with important physiological functions for the therapy of human cardio/cerebro-vascular diseases.

Relaxant Effect of 4-Aminopyridine on the Mesenteric Artery of Rat

  • Kim, Se-Hoon;Lee, Tae-Im
    • The Korean Journal of Physiology and Pharmacology
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    • v.4 no.6
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    • pp.463-469
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    • 2000
  • It has been well known that 4-aminopyridine (4-AP) has an excitatory effect on vascular smooth muscle due to causing membrane depolarization by blocking $K^+-channel$. However, we observed that 4-AP had an inhibitory effect on the mesenteric artery of rat. Therefore, we investigated the mechanism of 4-AP-induced vasorelaxation. The mesenteric arcuate artery and its branches were isolated and cut into ring. The ring segment was immersed in HEPES-buffered solution and its isometric tension was measured. 4-AP $(0.1{\sim}10\;mM)$ induced a concentration-dependent relaxation, which was unaffected by NO synthase inhibitor, $N^G-nitro-L-arginine$ methylester $(100\;{\mu}M)$ or soluble guanylate cyclase inhibitor, methylene blue $(100\;{\mu}M).$ Glibenclamide $(100\;{\mu}M)$, ATP-sensitive $K^+$ channel blocker, did not exert any effect on the 4-AP-induced vasorelaxation. 4-AP relaxed the sustained contraction induced by 100 mM $K^+$ or $Ca^{2+}$ ionophore, A23187 $(100\;{\mu}M)$ in a dose-dependent manner. In addition, 4-AP significantly decreased the phasic contractile response to norepinephrine in the absence of extracellular $Ca^{2+}$. However, 4-AP did not block the $^{45}Ca$ influx of rat aorta. From the above results, we suggest that 4-AP may not block the $Ca^{2+}$ influx through $Ca^{2+}-channel,$ but act as a nonspecific vasorelaxant in arterial smooth muscle.

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Study on Oriental Prescription for Medicinal Food Applications -Effects and Mechanism of Saengmaegsan on the Relaxation of Contracted Artery and Regional Cerebral Blood Flow- (한약처방을 활용한 Medicinal Food의 개발에 관한 연구 - 생맥산이 수축동맥의 이완과 국소뇌혈류량에 미치는 효과 및 기전 -)

  • Park Sung-Hye;Kim Woon-Ju
    • Journal of the East Asian Society of Dietary Life
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    • v.15 no.5
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    • pp.606-612
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    • 2005
  • This study was performed to provide basic data that predict the application of Saengmaegsan(SMS) as medicinal food. SMS has been used in oriental medicine for many years as a therapeutic agent for cerebral disease. We examined the effects of SMS on physiological function in isolated abdominal aorta and femoral artery from rabbit and measured the changes of regional cerebral hood flow(rCBF), which was continually monitored by laser-doppler flowmeter and pressure transducer in anesthetized adult Spargue-Dawley rats through the data acquisition system composed of MacLab and Macintosh computer. The contraction forces by injection of norephinephrine in isolated abdominal aorta and femoral artery were significantly decreased in each concentration of SMS treatment compared with control. rCBF was increased by SMS in a dose-dependent manner. These results suggest that SMS causes a diverse response of rCBF and arterial diameter. These mechanism in rCBF increase may be mediated by prostaglandis, cyclic GMP and adrenergic $\beta-receptor$. Also mechanism in artery contraction decrease is also mediated by prostaglandis and cyclic GMP. These results indicate that SMS can be nsed as a safe and clinically applicable as a supplementation of diet therapy for cerebral cardiovascular disease patients.

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A Study on Estimation of Systolic Blood Pressure using PTT (PTT를 이용한 수축기 혈압의 측정에 관한 연구)

  • Park E. K.;Lee S. M.;Han Y. H.;Lee J. Y.;Kwon S. Y.;Kim I. Y.;Kim Sun I.
    • Journal of Biomedical Engineering Research
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    • v.25 no.6
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    • pp.605-609
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    • 2004
  • Blood pressure (BP) is one of the important physiological parameters for diagnosing cardiovascula diseases by means of noninvasive method. Existing noninvasive methods for measuring arterial BP have to use cuff and difficult in measuring arterial BP continuously. Systolic blood pressure (SBP) and pulse transit time (PTT) have a kind of inverse relationship. We acquired PTT data when subjects were in relaxation and also after exercise. We performed the linear regression analysis for making the regression equations for each subject and the regression equation for all subjects. We compared the estimated SBP with the measured SBP to check the accuracy of our regression equations. From the result, the regression equations for each subject was appropriate according to the American National Standards Institute of the Association of the Advancement of Medical Instrument (ANSI/AAMI) which says that BP devices should have ±5mmHg mean of error and 8mmHg standard deviation of error. However, the regression equation for all subjects was not proper to ANSI/AAMI recommendation. The result means that, without cuff, we can continuously estimate each subject's SBP through PTT and indivisual calibration.

Effects of HwangRyunHaeDok-Tang and Constituent Herbs on a Contracted Artery of Rabbit (황련해독탕(黃連解毒湯)이 가토(家兎)의 혈관긴장성조절(血管緊張性調節)에 미치는 영향(影響))

  • Nam Chang-Gyu;Kim Ho-Hyun;Jeong Chan-Gil;Sung Hyun-Jea;Kwon Oh-Yul
    • The Journal of Internal Korean Medicine
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    • v.24 no.2
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    • pp.220-232
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    • 2003
  • Objective : The purpose of this study was to analyze the effects of HwangRyunHaeDok-Tang and combinations of constituent herbs on the arterial contraction. Methods : In order to investigate the effects Scutellariae Radix. Coptidis Rhizoma, Phellodendri Cortex and Gardeniae Fructus, in which one of them, two of them, and all of them, were used to exam. Results : The results were summarized as follows; 1. HwangRyunHaeDok-Tang significantly inhibited the contraction of artery induced by Norepinephrine(NE). However the atonic effect was slightly blunted when the vascular endothelial cell was removed. No significant change in the atonic effect of HwangRyunHaeDok-Tang was found when $_L-NNA$ was used as a preliminary treatment. These results indicate that the vascular atonic effect by HwangRyunHaeDok-Tang is slightly dependent on the endothelial cell, and that the HwangRyunHaeDok-Tang works directly to the vascular smooth muscle in creating the vascular atonic effect. 2. The pretreatment of HwangRyunHaeDok-Tang extract significantly inhibited the contractile response to additive application of $Ca^{2+}$ in the strips which were contracted by NE in $Ca^{2+}$-free solution. 3. HwangRyunHaeDok-Tang extract increased the contraction of arterial smooth muscle induced by KCl. Therefore, it can be concluded that HwangRyunHaeDok-Tang may block the NE-receptor or receptor-operated $Ca^{2+}$ channel. 4. It was determined that Scutellariae Radix, Coptidis Rhizoma and Phellodendri Cortex among the ingredients of HwangRyunHaeDok-Tang have a vascular atonic effect. In addition, those ingredients plays a role in strengthening the atonic effect by working with other herbal medicines. Gardeniae Fructus causes the blood vessel to contract. but it does not influence the atonic effects of other herbal medicines. However Gardeniae Fructus tends to inhibit the vascular atonic effect of Phellodendri Cortex. Conclusion : Based on the above results, it can be said that HwangRyunHaeDok-Tang can be applied to cure hypertension considering those three herbs have significant effects of relaxation.

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The Functional Effects of Fermented Pine Needle Extract (솔잎착즙액의 발효에 따른 기능성 효과)

  • Park, Ga-Young;Li, Hongxian;Hwang, In-Deok;Cheong, Hyeon-Sook
    • KSBB Journal
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    • v.21 no.5
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    • pp.376-383
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    • 2006
  • Pine needle(Pinus densiflora sieb, et zucc) extract has been used to improve cardiovascular disorders, detoxification of nicotine, the infirmities of age and curing diseases of unidentified symptoms. It has various useful components including amino acids, vitamin C, terpenoids and chlorophyll. In this study we have identified 8 different yeast strains that are developed spontaneously causing self fermentation in the extract. The self-fermented pine extract(SFPE) inhibited the growth of some bacterial strains like E. coli, Bacillus subtilis and Staphylococcus aureus. The SFPE($0.2{\mu}{\ell}/ml{\sim}0.3{\mu}{\ell}/ml$) showed 90% NBT superoxide scavenging activities which is similar for all tested samples of different ages. The 7 years old SFPE(0.15 mg/ml and 0.3 mg/ml) caused relaxation of spontaneous contraction and relaxation rhythm of thoracic arterial tissues from rat. Therefore, SFPE has useful effects such as antibacterial, antioxidant and improved blood circulation and could be a good source of functional food development.

Magnesium-induced Relaxation in Rat Aorta (Magnesium에 의한 흰쥐 대동맥 이완)

  • Oh, Sung-suck;Lee, Sang-woo;Kang, Hyung-sub;Kim, Jin-shang
    • Korean Journal of Veterinary Research
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    • v.43 no.3
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    • pp.373-382
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    • 2003
  • Magnesium ion ($Mg^{2+}$) is a vasodilator, but little is known about its mechanism of action on vascular system. In vitro, extracellular magnesium sulfate ($MgSO_4$) produced relaxation in phenylephrine (PE) or high KCl-precontracted isolated rat thorocic aorta with (+E) or without (-E) endothelium in a concentration-dependent manner. The $MgSO_4$-induced relaxations were not affected by removal of the endothelium. Pretreatment of +E or -E aortic rings with nitric oxide synthase (NOS) inhibitors ($20{\mu}M$ L-NNA, $100{\mu}M$ L-NAME, $1{\mu}M$ dexamethasone and $400{\mu}M$ aminoguanidine), cyclooxygenase inhibitor ($10{\mu}M$ indomethacin), guanylate cyclase inhibitors ($10{\mu}M$ ODQ and $30{\mu}M$ methylene blue) and $Ca^{2+}$ transport blocker ($10{\mu}M$ ryanodine) did not affect the relaxant effects of $MgSO_4$. $Ca^{2+}$ channel blockers ($0.3{\mu}M$ nifedipine and $0.5{\mu}M$ veropamil) completely decreased the relaxant effects of $MgSO_4$ in +E and -E aortic rings. However, in $Ca^{2+}$-free medium, $MgSO_4$-induced vasorelaxation was potentiated and this response was inhibited by nifedipine. Protein kinase C (PKC) inhibitors ($1.0{\mu}M$ staurosporine, $0.5{\mu}M$ tamoxifen and $0.1{\mu}M$ H7) or PLC inhibitor ($100{\mu}M$ NCDC) markedly decreased the relaxant effects of $MgSO_4$ in +E and -E aortic rings. In vivo, infusion of $MgSO_4$ elicited significant decreases in arterial blood pressure. After intravenous injection of nifedipine ($150{\mu}g/kg$) and NCDC (3 mg/kg), infusion of $MgSO_4$ inhibited the $MgSO_4$-lowered blood pressure markedly. However, after introvenous injection of saponin (15 mg/kg), L-NNA (3 mg/kg), L-NAME (5 mg/kg), indomethacin (2 mg/kg), methylene blue (15 mg/kg) and aminoguanidine (10 mg/kg) failed to inhibit it. These results suggest that endothelial NQ-cGMP or prostaglandin pathway is not involved in vasorelaxant or hypotensive action of $Mg^{2+}$ and that these effects are due to the inhibitory action of $Mg^{2+}$ on the $Ca^{2+}$ channel or PLC-PKC pathway, and are due to the competitive influx of $Mg^{2+}$ and $Ca^{2+}$ through the $Ca^{2+}$ channel.

Mechanism of Membrane Hyperpolarization by Extracellular $K^+$ in Resistance-sized Cerebral Arterial Muscle Cell of Rabbit

  • Kim, Se-Hoon;Choi, Kun-Moo;Kim, Hoe-Suk;Jeon, Byeong-Hwa;Chang, Seok-Jong
    • The Korean Journal of Physiology and Pharmacology
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    • v.3 no.1
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    • pp.1-10
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    • 1999
  • We sought to find out the mechanism of vascular relaxation by extracellular $K^+$ concentration $([K^+]_o)$ in the cerebral resistant arteriole from rabbit. Single cells were isolated from the cerebral resistant arteriole, and using voltage-clamp technique barium-sensitive $K^+$ currents were recorded, and their characteristics were observed. Afterwards, the changes in membrane potential and currents through the membrane caused by the change in $[K^+]_o$ was observed. In the smooth muscle cells of cerebral resistant arteriole, ion currents that are blocked by barium, 4-aminopyridine (4-AP), and tetraethylammonium (TEA) exist. Currents that were blocked by barium showed inward rectification. When the $[K^+]_o$ were 6, 20, 60, and 140 mM, the reversal potentials were $-82.7{\pm}1.0,\;-49.5{\pm}1.86,\;-26{\pm}1.14,\;-5.18{\pm}1.17$ mV, respectively, and these values were almost identical to the calculated $K^+$ equilibrium potential. The inhibition of barium-sensitive inward currents by barium depended on the membrane potential. At the membrane potentials of -140, -100, and -60 mV, $K_d$ values were 0.44, 1.19, and 4.82 ${\mu}M,$ respectively. When $[K^+]_o$ was elevatedfrom 6 mM to 15 mM, membrane potential hyperpolarized to -50 mV from -40 mV. Hyperpolarization by $K^+$ was inhibited by barium but not by ouabain. When the membrane potential was held at resting membrane potential and the $[K^+]_o$ was elevated from 6 mM to 15 mM, outward currents increased; when elevated to 25 mM, inward currents increased. Fixing the membrane potential at resting membrane potential and comparing the barium-sensitive outward currents at $[K^+]_o$ of 6 and 15 mM showed that the barium- sensitive outward current increased at 15 mM $K^+.$ From the above results the following were concluded. Barium-sensitive $K^+$?channel activity increased when $[K^+]_o$ is elevated and this leads to an increase in $K^+-outward$ current. Consequently, the membrane potential hyperpolarizes, leading to the relaxation of resistant arteries, and this is thought to contribute to an increase in the local blood flow of brain.

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