• 제목/요약/키워드: Isolated rat heart

검색결과 173건 처리시간 0.027초

Peroxisome proliferator-activated receptor γ is essential for secretion of ANP induced by prostaglandin D2 in the beating rat atrium

  • Zhang, Ying;Li, Xiang;Liu, Li-Ping;Hong, Lan;Liu, Xia;Zhang, Bo;Wu, Cheng-Zhe;Cui, Xun
    • The Korean Journal of Physiology and Pharmacology
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    • 제21권3호
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    • pp.293-300
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    • 2017
  • Prostaglandin $D_2$ ($PGD_2$) may act against myocardial ischemia-reperfusion (I/R) injury and play an anti-inflammatory role in the heart. Although the effect of $PGD_2$ in regulation of ANP secretion of the atrium was reported, the mechanisms involved are not clearly identified. The aim of the present study was to investigate whether $PGD_2$ can regulate ANP secretion in the isolated perfused beating rat atrium, and its underlying mechanisms. $PGD_2$ (0.1 to $10{\mu}M$) significantly increased atrial ANP secretion concomitantly with positive inotropy in a dose-dependent manner. Effects of $PGD_2$ on atrial ANP secretion and mechanical dynamics were abolished by AH-6809 ($1.0{\mu}M$) and AL-8810 ($1.0{\mu}M$), $PGD_2$ and prostaglandin $F2{\alpha}$ ($PGF2{\alpha}$) receptor antagonists, respectively. Moreover, $PGD_2$ clearly upregulated atrial peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) and the $PGD_2$ metabolite 15-deoxy-${\Delta}12$, 14-$PGJ_2$ (15d-$PGJ_2$, $0.1{\mu}M$) dramatically increased atrial ANP secretion. Increased ANP secretions induced by $PGD_2$ and 15d-$PGJ_2$ were completely blocked by the $PPAR{\gamma}$ antagonist GW9662 ($0.1{\mu}M$). PD98059 ($10.0{\mu}M$) and LY294002 ($1.0{\mu}M$), antagonists of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling, respectively, significantly attenuated the increase of atrial ANP secretion by $PGD_2$. These results indicated that $PGD_2$ stimulated atrial ANP secretion and promoted positive inotropy by activating $PPAR{\gamma}$ in beating rat atria. MAPK/ERK and PI3K/Akt signaling pathways were each partially involved in regulating $PGD_2$-induced atrial ANP secretion.

흰쥐 타액선내에서의 DENDROASPIS NATRIURETIC PEPTIDE(DNP)의 분포 (Localization of Dendroaspis natriuretic peptide (DNP) in the rat salivary glands)

  • 김재곤;이영수;백병주;박병건
    • 대한소아치과학회지
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    • 제28권3호
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    • pp.447-463
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    • 2001
  • Dendroaspis natriuretic peptide(DNP)는 Dendroaspis angusticeps의 뱀독으로부터 추출된 natriuretic peptide의 새로운 일원으로서, 사람의 혈장과 심방 근육에 존재하고 실험동물에서 혈관확장과 이뇨작용을 나타내는 것으로 알려져있다. 그러나 아직까지 심장 이외의 다른 기관내에 DNP가 존재하는지 또한 이들이 현재까지 알려진 기능 이 외의 또다른 생리적 기능을 나타내는 지의 여부는 아직 확실하게 밝혀져 있지 않다. 타액전 내에서 DNP의 기능을 규명하기 위한 전단계로, 먼저 흰쥐의 타액선내에 DNP가 존재하는지를 면역조직화학법을 이용하여 알아보았고 또한 DNP의 수용체가 타액전 또는 구강점막내에 존재하는 지의 여부를 생체외 방사선자기법을 이용하여 알아보았다. DNP의 면역반응은 악하선과 설하선 및 이하선에서 주로 도관부위에서 관찰되었고, 선포부위에서는 관찰되지 않았다. atrial natriuretic peptide(ANP)의 면역반응 역시 악하선과 설하선 및 이하선에서 DNP 면역반응과 유사하게 주로 도관부위에서 관찰되었다. DNP에 특이한 수용체가 타액선에는 저밀도로 존재한 반면 경구개와 혀 점막상피부위에서는 고밀도로 존재하였다. 경구개와 혀 점막상피부위의 DNP수용체는 주로 상피의 기저층과 기저층에 인접한 유극세포층에 국한되어 존재하는 것을 미세방사선자기법을 통하여 알 수 있었다. 이러한 결과로 볼 때 DNP가 타액선과 구강점막 부위에서 어떠한 생리적 기능을 나타낼 것으로 여겨지는데, 특히 구강점막 부위에서는 점막상피세포의 성장과 성숙과정에 관여하리라 추정된다.

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Gypenoside XVII protects against myocardial ischemia and reperfusion injury by inhibiting ER stress-induced mitochondrial injury

  • Yu, Yingli;Wang, Min;Chen, Rongchang;Sun, Xiao;Sun, Guibo;Sun, Xiaobo
    • Journal of Ginseng Research
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    • 제45권6호
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    • pp.642-653
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    • 2021
  • Background: Effective strategies are dramatically needed to prevent and improve the recovery from myocardial ischemia and reperfusion (I/R) injury. Direct interactions between the mitochondria and endoplasmic reticulum (ER) during heart diseases have been recently investigated. This study was designed to explore the cardioprotective effects of gypenoside XVII (GP-17) against I/R injury. The roles of ER stress, mitochondrial injury, and their crosstalk within I/R injury and in GP-17einduced cardioprotection are also explored. Methods: Cardiac contractility function was recorded in Langendorff-perfused rat hearts. The effects of GP-17 on mitochondrial function including mitochondrial permeability transition pore opening, reactive oxygen species production, and respiratory function were determined using fluorescence detection kits on mitochondria isolated from the rat hearts. H9c2 cardiomyocytes were used to explore the effects of GP-17 on hypoxia/reoxygenation. Results: We found that GP-17 inhibits myocardial apoptosis, reduces cardiac dysfunction, and improves contractile recovery in rat hearts. Our results also demonstrate that apoptosis induced by I/R is predominantly mediated by ER stress and associated with mitochondrial injury. Moreover, the cardioprotective effects of GP-17 are controlled by the PI3K/AKT and P38 signaling pathways. Conclusion: GP-17 inhibits I/R-induced mitochondrial injury by delaying the onset of ER stress through the PI3K/AKT and P38 signaling pathways.

급성 저산소증 상태에서 심장 내 전사인자 NF-κB의 기능 (Role of the Nuclear Transcription Factor NF-κB Caused by Acute Hypoxia in the Heart)

  • 주찬웅;정우석;김재철;이호근
    • Clinical and Experimental Pediatrics
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    • 제45권9호
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    • pp.1106-1113
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    • 2002
  • 목 적: 전사인자 $NF-{\kappa}B$는 스트레스 등으로부터 세포 자멸사를 조절하여 적응을 유지하는 기본적인 분자로 인식되고 있다. 저산소증 상태는 많은 심장병에서 동반되는 병변으로 성장인자 VEGF와 IGF-I는 저산소증 시에 심장을 보호하는 작용을 할 것으로 추측되고 있다. 본 연구에서는 저산소증과 같은 자극으로부터 심장의 보호 기능이 추정된 $NF-{\kappa}B$의 발현과 함께 VEGF와 IGF-I의 발현 연관성을 검토하여 분자 생물학적인 기전을 이해하고자 하였다. 방 법 : 실험동물로 Sprague Dawley rat을 이용하여, 저산소 자극은 8%의 산소와 92% 질소를 hypoxic chamber로 관류시키며 유도하였다. 심장에 대한 저산소증 자극 후 심근세포로부터 측정 인자들과 관련된 핵 내 단백질, 전단백질 그리고 mRNA를 분리하였다. 핵 내의 전사인자는 EMSA로 측정하였으며, VEGF와 IGF-I의 발현은 competitive-PCR, Western hybridization, Northern hybridization으로 확인하였다. 또한 이러한 성장인자의 발현과 관련된 $NF-{\kappa}B$의 기능을 확인하기 위하여 $NF-{\kappa}B$의 핵 내 이동 억제제인 DDTC를 전 처치로 복강 내 주사하여 그에 따른 VEGF 및 IGF-I의 발현 양상을 비교하였다. 결 과 : 저산소 자극 후에 심근 세포 내에 전사인자 $NF-{\kappa}B$, AP-1, NF-ATc의 활성이 증가되었다. VEGF와 IGF-I의 발현도 저산소증 자극 시 증가되었지만, DDTC 전 처치에 의한 $NF-{\kappa}B$의 핵 내 이동 차단 후 이들 인자의 발현은 의의 있게 감소하였다. 결 론 : 전사인자 $NF-{\kappa}B$는 저산소증 상태에서 그 활성이 증가하고 저산소증 상태와 같은 심장에 대한 이상 자극 시 VEGF와 IGF-I의 발현을 증가시켜 심장을 보호하는 것으로 추정된다.

허혈/재관류 심장의 산화손상에서 미토콘드리아의 역할 (Role of Mitochondria in Oxidative Damage of Post-Ischemic Reperfused Hearts)

  • 박종완;전양숙;김명석
    • 대한약리학회지
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    • 제32권2호
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    • pp.201-209
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    • 1996
  • Restoration of the blood flow after a period of ischemia is accompanied by generation of toxic oxygen radicals. This phenomenon may account for the occurrence of reperfusion-mediated tissue injury in ischemic hearts. In in vitro studies, although oxygen radicals can be generated from a variety of sources, including xanthine oxidase system, activated leucocytes, mitochondria and others, the most important source and mechanism of oxygen radical production in the post-ischemic reperfused hearts is unclear. In the present study, we tested the hypothesis that the respiratory chain of mitochondria might be an important source of oxygen radicals which are responsible for the development of the reperfusion injury of ischemic hearts. Langendorff-perfused, isolated rat hearts were subjected to 30 min of global ischemia at $37^{\circ}C$, followed by reperfusion. Amytal, a reversible inhibitor of mitochondrial respiration, was employed to assess the mitochondrial contributions to the development of the reperfusion injury. Intact mitochonria were isolated from the control and the post-ischemic reperfused hearts. Mitochondrial oxygen radical generation was measured by chemiluminescence method and the oxidative tissue damage was estimated by measuring a lipid peroxidation product, malondialdehyde(MDA). To evaluate the extent of the reperfusion injury, post-ischemic functional recovery and lactate dehydrogenase(LDH) release were assessed and compared in Amytal-treated and -untreated hearts. Upon reperfusion of the ischemic hearts, MDA release into the coronary effluent was markedly increased. MDA content of mitochondria isolated from the post-ischemic reperfused hearts was increased to 152% of preischemic value, whereas minimal change was observed in extramitochondrial fraction. The generation of superoxide anion was increased about twice in mitochondria from the reperfused hearts than in those from the control hearts. Amytal inhibited the mitochondrial superoxide generation significantly and also suppressed MDA production in the reperfused hearts. Additionally, Amytal prevented the contractile dysfunction and the increased release of LDH observed in the reperfused hearts. In conclusion, these results indicate that the respiratory chain of mitochondria may be an important source of oxygen radical formation in post-ischemic reperfused hearts, and that oxygen radicals originating from the mitochondria may contribute to the development of myocardial reperfusion injury.

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Modulation of ATP-Induced Activation of the Muscarinic $K^+$ Channel Activity by Protein Kinase C

  • Kim, Yang-Mi;Park, Hong-Ki;Han, Jae-Hee;Park, Choon-Ok;Hong, Seong-Geun
    • The Korean Journal of Physiology and Pharmacology
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    • 제2권6호
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    • pp.743-752
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    • 1998
  • The atrial acetylcholine-activated $K^+\;(K_{ACh})$ channel is gated by the pertussis toxin-sensitive inhibitory G $(G_K)$ protein. Earlier studies revealed that ATP alone can activate the $K_{ACh}$ channel via transphosphorylation mediated by nucleoside-diphosphate kinase (NDPK) in atrial cells of rabbit and guinea pig. This channel can be activated by various agonists and also modulated its function by phosphorylation. ATP-induced $K_{ACh}$ channel activation (AIKA) was maintained in the presence of the NDPK inhibitor, suggesting the existence of a mechanism other than NDPK-mediated process. Here we hypothesized the phosphorylation process as another mechanism underlying AIKA and was undertaken to examine what kinase is involved in atrial cells isolated from the rat heart. Single application of 1 mM ATP gradually increased the activity of $K_{ACh}$ channels and reached its maximum $40{\sim}50$ sec later following adding ATP. AIKA was not completely reduced but maintained by half even in the presence of NDPK inhibitor. Neither ADP nor a non-hydrolyzable ATP analogue, AMP-PNP can cause AIKA, while a non-specific phosphatase, alkaline phosphatase blocked completely AIKA. PKC antagonists such as sphingosine or tamoxifen, completely blocked AIKA, whereas PKC catalytic domain increased AIKA. Taken together, it is suggested that the PKC-mediated phosphorylation is partly involved in AIKA.

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스트레스성 자극에 의한 항산화효소 유도와 허혈/재관류 심장 보호효과 (Effects of in vivo-stresses on the Activities of the Myocardial Antioxidant Enzymes and the Ischemia-Reperfusion Injury in Rat Hearts)

  • 박종완;김영훈;김명석
    • Toxicological Research
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    • 제11권1호
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    • pp.161-168
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    • 1995
  • It has been found that various stress challenges induce the myocardial antioxidant enzymes and produce an acquisition of the cellular resistance to the ischemic injury in animal hearts. Most of the stresses, however, seem to be guite dangerous to an animal's life. In the present study, therefore, we tried to search for safely applicable stress modalities which could lead to the induction of antioxidant enzymes and the production of myocardial tolerance to the ischemia-reperfusion injury. Male Sprague-Dawley rats (200-250 g) were exposed to various non-fatal stress conditions, i.e., hyperthermia (environmental temperature of $42^{\circ}C$ for 30 min, non-anesthetized animal), iramobilization (60 min), treadmill exercise (20 m/min, 30min), swimming (30 min), and hyperbaric oxyflenation (3 atm, 60 min), once a day for 5 days. The activities of myocardial antioxidant enzymes and the ischemia-reperfusion injury of isolated hearts were evaluated at 24 hr after the last application of the stresses. The activities of antioxidant enzymes, superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase (G6PD), were assayed in the freshly excised ventricular tissues. The ischemia-reperfusion injury was produced by 20 min-global ischemia followed by 30 min-reperfusion using a Langendorff perfusion system. In swimming and hyperbaric oxygenation groups, the activities of SOD and G6PD increased significantly and in the hyperthermia group, the catalase activity was elevated by 63% compared to the control. The percentile recoveries of cardiac function at 30 min of the post-ischemic reperfusion were 55.4%, 73.4%, and 74.2% in swimming, the hyperbaric oxygenation and the hyperthermia groups, respectively. The values were significantly higher than that of the control (38.6%). In additions, left ventricular end-diastolic pressure and lactate dehydrogenase release were significantly reduced in the stress groups. The results suggest that the antioxidant enzymes in the heart could be induced by the apparently safe in vivo-stresses and this may be involved in the myocardial protection from the ischemia-reperfusion injury.

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Molecular Cloning and Expression of cDNAs Encoding Mouse $Gal{\beta}$1,3(4)GlcNAc ${\alpha}$2,3-Sialyltransferase (mST3Gal III) and $Gal{\beta}$1,4(3)GlcNAc ${\alpha}$2,3-Sialyltransferase (mST3GaI IV)

  • Kim, Kyoung-Sook;Kim, Cheorl-Ho;Shin, Deug-Yong;Lee, Young-Choon
    • BMB Reports
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    • 제30권2호
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    • pp.95-100
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    • 1997
  • Two kinds of cDNA encoding mouse $Gal{\beta}$1,3(4)GlcNAc ${\alpha}$2,3-sialyltransferase (mST3Gal III) and $Gal{\beta}$1,4(3)GlcNAc ${\alpha}$2,3-sialyltransferase (mST3Gal IV) were isolated from mouse brain cDNA library by means of a PCR-based approach. The cDNA sequences included an open reading frame coding for proteins of 374 and 333 amino acids, respectively, and the primary structure of these enzymes suggested a putative domain structure consisting of four regions, like that in other glycosyltransferases. The deduced amino acid sequences of mST3GaI III and IV showed a 98% and 89% identity with rat ST3GaI III and human ST3Gal IV, respectively. Northern analysis indicated that the expression of mST3Gal III mRNA was abundant in heart, liver and adult brain, while that of mST3GaI IV mRNA was detected in all tissues tested except for testis, but the level was the highest in liver. Soluble forms of mST3GaI III and IV transiently expressed in COS cells exhibited enzyme activity toward acceptor substrates containing the terminal either $Gal{\beta}$1,3GlcNAc or $Gal{\beta}$1,4GlcNAc sequences. The substrate preferences of both enzymes were stronger for tetrasaccharides than for disaccharides.

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General Pharmacology of Artesunate, a Commonly used Antimalarial Drug: Effects on Central Nervous, Cardiovascular, and Respiratory System

  • Lee, Hyang-Ae;Kim, Ki-Suk;Kim, Eun-Joo
    • Toxicological Research
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    • 제26권3호
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    • pp.223-232
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    • 2010
  • Artesunate, a semi-synthetic derivative of artemisinin, is used primarily as a treatment for malaria. Its effects on the central nervous system, general behavior, and cardiovascular, respiratory, and other organ systems were studied using mice, rats, guinea pigs, and dogs. Artesunate was administered orally to mice at doses of 125, 250, and 500 mg/kg and to rats and guinea pigs at 100, 200, and 400 mg/kg. In dogs, test drugs were administered orally in gelatin capsules at doses of 50, 100, and 150 mg/kg. Artesunate induced insignificant changes in general pharmacological studies, including general behavior, motor coordination, body temperature, analgesia, convulsion modulation, blood pressure, heart rate (HR), and electrocardiogram (ECG) in dogs in vivo; respiration in guinea pigs; and gut motility or direct effects on isolated guinea pig ileum, contractile responses, and renal function. On the other hand, artesunate decreased the HR and coronary flow rate (CFR) in the rat in vitro; however, the extent of the changes was small and they were not confirmed in in vivo studies in the dog. Artesunate increased hexobarbital-induced sleeping time in a dose-related manner. Artesunate induced dose-related decreases in the volume of gastric secretions and the total acidity of gastric contents, and induced increases in pH at a dose of 400 mg/kg. However, all of these changes were observed at doses much greater than clinical therapeutic doses (2.4 mg/kg in humans, when used as an anti-malarial). Thus, it can be concluded that artesunate is safe at clinical therapeutic doses.

Cholinomimetic Properties of a Water-Soluble Fraction from Mulberry Leaves in Rats

  • Lee, Ju-Seon;Chung, Sung-Hyun;Lee, Yong-Sup;Jin, Chang-Bae
    • Biomolecules & Therapeutics
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    • 제13권1호
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    • pp.26-31
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    • 2005
  • The present study examined effects of a water-soluble fraction from mulberry leaves (ML water fraction) on the circulatory and autonomic nervous systems, which were compared with those of acetylcholine (ACh) used as a reference drug in order to elucidate its mechanism of action. Intravenous administration of ACh or a ML water fraction produced temporary depressor and tachycardiac responses in a dose-dependent manner in unrestrained, conscious Sprague-Dawley rats. The systemic hemodynamic effects of ACh and a ML water fraction were almost completely blocked by pretreatment with atropine, a muscarinic antagonist. The depressor responses to ACh and a ML water fraction were slightly enhanced and prolonged by pretreatment with neostigmine, an anticholinesterase, whereas the tachycardiac responses were remarkably blocked by pretreatment with pentolinium, a ganglionic blocking agent. In vitro experiments using the ileum isolated from rats showed that ACh and a ML water fraction increased ileal contractility in a dose-dependent manner. The increases in ileal contractility were also completely abolished in the presence of atropine. Finally, the specific binding of [$^3H$]quinuclidinyl benzilate, a muscarinic antagonist, to rat cortical synaptic membranes was inhibited by a ML water fraction in a concentration-dependent manner with an IC$_{50}$ value of 9.5 mg/ml. The results suggest that the effects of a ML water fraction are mediated through direct stimulation of muscarinic cholinergic receptors by unknown cholinomimetic substance(s) contained in that fraction.