Pharmacological Characterization of Vasorelaxant Effects of BMS-180448, a Novel Cardioselective ATP-Sensitive Potassium Channel Opener, in Rat Aorta
スポンサーリンク
概要
- 論文の詳細を見る
This study was designed to characterize vasorelaxant effects of BMS-180448 ((3S-trans)-N-(4-chlorophenyl)-N-cyano-N-(6-cyano-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-4-yl)), a prototype cardioselective ATP-sensitive potassium channel opener, in rat aorta. BMS-180448 relaxed phenylephrine-precontracted endothelium-intact aortic rings (IC50: 0.97 ± 0.29 μM), the effect being significantly attenuated by removal of functional endothelium (IC50: 1.95 ± 0.23 μM) and pretreatment with NG-nitro-<sc>L</sc>-arginine methyl ester (<sc>L</sc>-NAME) or methylene blue. BMS-180448 completely relaxed endothelium-denuded aorta contracted with phorbol 12,13-dibutyrate, PGF2α, and U46619 with a significantly greater potency (IC50: 0.069 ± 0.002, 0.055 ± 0.002, and 0.068 ± 0.008 μM, respectively, P<0.05) than that contracted with phenylephrine (1.95 ± 0.23 μM) or KCl (0.25 ± 0.08 μM), indicating potency change with the type of vasoconstrictor. BMS-180448 (1 – 3 μM) inhibited Ca2+ (0.5 – 2.5 mM)-induced contraction of endothelium-denuded aorta evoked in the presence of high KCl (65.4 mM), but had no effect on contraction induced by phenylephrine in Ca2+-free buffer. BMS-180448 (10 μM) increased cAMP level in aorta by approximately two-fold compared with the control, comparable to forskolin, an adenylate cyclase activator. These findings suggest that cardioselective BMS-180448 still exerts significant vasorelaxant activity in rat aorta contracted with various vasoconstrictors via multiple mechanisms including the blockade of extracellular Ca2+ influx through voltage-dependent channels and activation of the adenylate cyclase and nitric oxide pathway, with the possibility of hemodynamic implications in certain clinical conditions such as myocardial infarction and hypertension.
- 社団法人 日本薬理学会の論文
- 2003-07-01
著者
-
Yun Yeo-Pyo
College of Pharmacy, Chungbuk National University
-
Yoo Sung-eun
Medical Science Division Korea Research Institute Of Chemical Technology
-
Yoo S‐e
Korea Res. Inst. Of Chemical Technol. Daejon Kor
-
Yun Yeo-pyo
Coll. Of Pharmacy Chungbuk National Univ.
-
Yun Yeo-pyo
College Of Pharmacy Research Center For Bioresource And Health Chungbuk National University
-
Yun Y‐p
Chungbuk National Univ. Cheongju Kor
-
Yun Yeo-pyo
College Of Pharmacy Chungbuk National University
-
Shin Hwa-sup
Department Of Applied Biochemistry Division Of Life Science College Of Biomedical And Health Science
-
YOO Sung-Eun
Bio-organic Division, Korea Research Institute of Chemical Technology
-
Park Yang-su
College Of Pharmacy Research Center For Bioresource And Health Chungbuk National University
-
Jin Yong-ri
College Of Pharmacy Research Center For Bioresource And Health Chungbuk National University
-
SHIN Hwa-Sup
Division of Life Science, College of Natural Sciences, Konkuk University
-
Yun Yeo-pyo
College Of Pharmacy Cbitrc College Of Pharmacy And Medical Research Center Chungbuk National Univers
-
Yun Yeo-Pyo
College of Pharmacy and Medical Research Center, Chungbuk National University
関連論文
- Potent inhibition of platelet-derived growth factor-stimulated rat aortic vascular smooth muscle cell cycle and proliferation by (2E)-3-(4-hydroxy-3-methoxyphenyl)phenylpro-2-en-1-one, a newly synthesized benzylideneacetophenone derivative
- Potent Inhibition of Platelet-Derived Growth Factor-Stimulated Rat Aortic Vascular Smooth Muscle Cell Cycle and Proliferation by (2E)-3-(4-hydroxy-3-methoxyphenyl)phenylpro-2-en-1-one, a Newly Synthesized Benzylideneacetophenone Derivative
- Corynoxeine Isolated from the Hook of Uncaria rhynchophylla Inhibits Rat Aortic Vascular Smooth Muscle Cell Proliferation through the Blocking of Extracellular Signal Regulated Kinase 1/2 Phosphorylation(Pharmacology)
- KR-31761, a Novel K^+_-Channel Opener, Exerts Cardioprotective Effects by Opening Both Mitochondrial K^+_ and Sarcolemmal K^+_ Channels in Rat Models of Ischemia/Reperfusion-Induced Heart Injury
- Effects of [5-(2-Methoxy-5-fluorophenyl)furan-2-ylcarbonyl]guanidine (KR-32560), a Novel Sodium/Hydrogen Exchanger-1 Inhibitor, on Myocardial Infarct Size and Ventricular Arrhythmias in a Rat Model of Ischemia/Reperfusion Heart Injury
- Inhibitory Effects of BST406, a Newly Synthesized Benzylideneacetophenone Derivative, on Abnormal Vascular Smooth Muscle Cell Proliferation
- Genistein Inhibits Rat Aortic Smooth Muscle Cell Proliferation Through the Induction of p27^
- Antiplatelet Effect of NQ12 : a Possible Mechanism Through the Arachidonic Acid Cascade
- Cudratricusxanthone A Isolated from the Root Bark of Cudrania tricuspidata Inhibits the Proliferation of Vascular Smooth Muscle Cells through the Suppression of PDGF-Receptor Beta Tyrosine Kinase(Pharmacology)
- Cardioprotective Effects of KR-30450, a Novel K^+_ Opener, and Its Major Metabolite KR-30818 on Isolated Rat Hearts
- Inhibitory Effects of Anti-Inflammatory Drugs on Interleukin-6 Bioactivity
- Sauchinone Attenuates Oxidative Stress-Induced Skeletal Muscle Myoblast Damage through the Down-Regulation of Ceramide
- Pharmacological Characterization of Vasorelaxant Effects of BMS-180448, a Novel Cardioselective ATP-Sensitive Potassium Channel Opener, in Rat Aorta
- Inhibitory Effects of Docetaxel on Platelet-Derived Growth Factor (PDGF)-BB–Induced Proliferation of Vascular Smooth Muscle Cells Through Blocking PDGF-Receptor β Phosphorylation
- Antiplatelet and Antithrombotic Activities of NQ301,2-Chloro-3-(4-acetophenyl)-amino-1,4-naphthoquinone
- Inverse Relationship between Adipocyte Differentiation and Ceramide Level in 3T3-L1 Cells
- Antiplatelet Effect of 2-Chloro-3-(4-acetophenyl)-amino-1, 4-naphthoquinone(NQ301) : A Possible Mechanism through Inhibition of Intracellular Ca^Mobilization
- FUMONISIN-INDUCED ELEVATION OF FREE SPHINGANINE AND CELL CONFLUENCY ARE INVERSELY CORRELATED IN LLC-PK CELLS
- Inhibitory Effects of Docetaxel on Platelet-Derived Growth Factor (PDGF)-BB-Induced Proliferation of Vascular Smooth Muscle Cells Through Blocking PDGF-Receptor β Phosphorylation
- Clitocybin A, a Novel Isoindolinone, From the Mushroom Clitocybe aurantiaca, Inhibits Cell Proliferation Through G1 Phase Arrest by Regulating the PI3K/Akt Cascade in Vascular Smooth Muscle Cells
- JJK694, a Synthesized Obovatol Derivative, Inhibits Platelet Activation by Suppressing Cyclooxygenase and Lipoxygenase Activities