• 생명과학회지
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• 제32권2호
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• pp.175-188
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• 2022

혈관과 섬유증 기관들의 평활근과 세포외기질에 대한 릴랙신의 조절기능이 입증되어왔다. 본 총설에서는 저항성 소동맥과 방광을 포함한 섬유증 기관들의 세포외기질에 작용하는 릴랙신의 다양한 기전들을 고찰한다. 릴랙신은 혈관 평활근육의 수축을 억제하고, 콜라겐과 같은 세포외기질의 구성성분들을 감소키켜 혈관벽의 수동적 신전성을 증가시킴으로써, 혈관확장을 유도한다. 릴랙신이 동맥의 혈관확장을 유도하는 주된 세포기전은 RXFP1/PI3K의 활성화, Akt 인산화 및 eNOS 활성화를 통한 내피세포-의존성 산화질소의 생성에 의해 매개된다. 추가적으로, 릴랙신은 또한 다른 대체경로들을 작동하여 신장과 장간막 동맥의 혈관확장을 증가시킨다. 신장 소동맥에서, 릴랙신은 내피세포의 MMPs 및 EtB 수용체의 활성화와 VEGF 및 PlGF의 생성을 촉진하여, 평활근의 수축성과 콜라겐의 침착을 억제함으로써 혈관확장을 초래한다. 이와 달리, 장간막 소동맥에서, 릴랙신은 bradykinin (BK)-유도 이완을 시간-의존적으로 증강시킨다. BK-매개 이완의 신속 증가는 IK_Ca 이온통로와 뒤이은 EDH 유발에 의존하는 반면, BK에 의한 지속적 이완은 COX 활성과 PGI₂에 의존한다. 릴랙신의 항섬유화 효과는 염증유발 면역세포의 침투, endothelial-to-mesenchymal transition (EndMT) 및 근섬유아세포의 분화와 활성을 억제하여 매개된다. 릴랙신은 또한 근섬유아세포 내 NOS/NO/cGMP/PKG-1 경로를 활성화하여, TGF-β1-유도 ERK1/2 및 Smad2/3 신호의 활성과 ECM 콜라겐의 침착을 억제한다.

• 비파괴검사학회지
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• 제25권4호
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• pp.262-267
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• 2005

전신마취시 경막외차단술은 수술 후 통증을 조절하는데 널리 이용되고 있다. 마취상태에서는 여러 가지 혈류역학적 파라미터의 변화가 있으며, 맥파전달시간은 이러한 혈류역학적 파라미터들에 의해 많은 영향을 받고 있다. 맥파전달시간은 경막외차단술을 병행한 전신마취와 일반적인 전신마취 후에 동맥혈관벽의 이완으로 인해 손가락과 발가락에서의 PTT가 변화한다. 본 연구에서는 경막외차단술을 병행한 전신마취와 일반적인 전신마취에서 손가락과 발가락 PTT의 변화를 각각 측정하였다. 더불어, 일반적인 전신마취와 경막외 차단술을 병행한 전신마취에서의 손가락과 발가락사이의 pTT변화를 비교하였다.

• Biomolecules & Therapeutics
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• 제25권5호
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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.

• The Korean Journal of Physiology and Pharmacology
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• 제4권6호
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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.

• 동아시아식생활학회지
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• 제15권5
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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.

• 대한의용생체공학회:의공학회지
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• 제25권6호
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• pp.605-609
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• 2004

혈압은 심혈관계 질환을 비침습적인 방법으로 진단할 때 사용하는 중요한 생리적 지표 중 하나이다. 보통 동맥 혈압을 측정하기 위해 사용되는 기존의 비침습적인 방법들은 커프를 사용해야 하며. 연속적 혈압 측정이 어렵다. 수축기 혈압과 맥파전달시간은 서로 반비례 관계를 가지고 있다. 실험은 피검자로부터 휴식을 통한 평온한 상태와 운동을 통한 격한 상태로부터 수축기 혈압과 맥파전달시간 데이터를 얻었다. 얻어진 데이터를 이용하여 각 피검자용 회귀식과 전체 피검자용 회귀식을 만들기 위해 선형회귀분석을 하였다. 만들어진 회귀식의 정확도를 검증하기 위해 측정한 수축기 혈압값과 예측한 수축기 혈압값을 비교하였다. 비교 결과, 각 피검자용 회귀식이 혈압계는 오차의 평균과 표준편차가 각각 ±5mmHg, 8 mmHg를 가져야 된다고 규정한 American National Standards Institute of the Association of the Advancement of Medical Instrument (ANSI/AAMI)에 적합하였다. 그러나 전체 피검자용 회귀식은 ANSI/AAMI의 규정에 적합하지 않았다. 이 결과는 맥파전달시간과 각 피검자에 맞는 초기 보정을 통해서 커프를 사용하지 않고, 연속적으로 수축기 혈압을 측정할 수 있음을 의미한다.

• 대한한방내과학회지
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• 제24권2호
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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.

• KSBB Journal
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• 제21권5호
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• pp.376-383
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• 2006

솔잎착즙액(PNE)은 엽록소 함유량(40.8 mg/100 g)이 높고 비타민 C도 다량함유(149 mg/100 g)하고 있어 기능성 식품으로 개발가능성이 높으며, 솔잎 발효액은 향미가 좋아지고 기능성이 높아져서 고부가가치가 크므로 발효의 조건과 활성도를 조사 분석하여 고기능성 솔잎발효액(SFPE)을 개발하고자 하였다. 솔잎자체발효(SFPE)에 관여하는 균을 발효단계에 따라 분리, 선발하고 동정하였다. GPYA배지에서 발효균을 스크린하여 Pichia galeiformis, Candida boidinii, Pichia species, Candida species1, Candida species2, Candida ooidensis, Saccharomyces cerevisiae, Candida karawaiewii를 선발하였으며, 발효가 진행됨에 따라 2년차에는 Candida boidinii, Candida species2, Candida ooidensis, Saccharomyces cerevisiae가 선발되었고, 3년차에는 Candida species1&2가 선발되어 Candida species2가 우점종으로 나타났다. 그러나 발효 4년차에는 어떤 균도 선발되지 않았다. Candida species2는 Candida ernobii와 99.65%의 homology를 보였다. E. coli, Bacillus subtilis와 Staphylococcus aureus에 대해서 SFPE를 농도별로 처리하였을 때 높은 항균활성을 확인하였다. SFPE 1, 4, 7의 항산화 활성은 $0.025{\mu}{\ell}/ml$의 농도로 처리하였을 경우 SFPE 1, 4, 7이 약 34.8%의 NBT scavenging의 활성을 보여주었고, $0.2{\mu}{\ell}/ml{\sim}0.3{\mu}{\ell}/ml$의 농도에서는 SFPE 1, 4, 7이 약 90%에 달하는 NBT scavenging 의 활성능력을 확인할 수 있었다. 또한 전기생리학적 실험을 통하여 솔잎발효액이 쥐의 혈관수축 이완에 미치는 효과를 분석한 결과 Phenylephrine(PE)($10^6M$)으로 유발된 수축반응에 대해 SFPE를 0.15 mg/ml과 0.3 mg/ml을 첨가하였을 때 혈관이 다시 이완되었으며, ATP 민감성 $K^+$ 채널 억제제인 glibenclamide($10^5M$)을 처리하였을 때 SFPE 7 효과가 나타나지 않은 것으로 보아 SFPE의 혈관 이완작용이 세포막 ATP-민감성 $K^+$ 통로를 활성화시켜 이루어짐을 확인하였다.

• 대한수의학회지
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• 제43권3호
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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.

• The Korean Journal of Physiology and Pharmacology
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• 제3권1호
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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.