| A cardioprotective agent of a novel calpain inhibitor, SNJ-1945, exerts beta1 actions on left ventricular mechanical work and energetics. | |
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MedLine Citation:
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PMID: 20511411 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have previously shown that a newly developed calpain inhibitor, SNJ-1945 (SNJ), with good aqueous solubility prevents the heart from KCl arrest-reperfusion injury associated with the impairment of total Ca(2+) handling by inhibiting the proteolysis of alpha-fodrin as a cardioplegia. The aim of the present study was to investigate certain actions of this calpain inhibitor, SNJ, on left ventricular (LV) mechanical work and energetics in cross-circulated excised rat hearts undergoing blood perfusion with 40 microM SNJ. Mean end-systolic pressure at midrange LV volume and systolic pressure-volume area (PVA) at mLVV (a total mechanical energy/beat) were significantly increased by SNJ perfusion (P < 0.01). Mean myocardial oxygen consumption per beat (Vo(2)) intercepts (Vo(2) for the total Ca(2+) handling in excitation-contraction coupling and basal metabolism) of Vo(2)-PVA linear relations were significantly increased (P < 0.01) with unchanged mean slopes of Vo(2)-PVA linear relations. Pretreatment with the selective beta(1)-blocker landiolol (10 microM) blocked these effects of SNJ perfusion. There were no significant differences in mean basal metabolic oxygen consumption among normal, 40 microM SNJ, and 10 microM landiolol + 40 microM SNJ groups. Our results indicate that water-soluble SNJ exerted positive actions on mechanical work and energetics mediated via beta(1)-adrenergic receptors associated with the enhancement of total Ca(2+) handling in excitation-contraction coupling and with unchanged contractile efficiency. In clinical settings, this pharmacological action of SNJ is beneficial as an additive agent for cardioplegia. |
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Authors:
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Yoshiro Yoshikawa; Guo-Xing Zhang; Koji Obata; Hiroko Matsuyoshi; Keiji Asada; Shigeki Taniguchi; Miyako Takaki |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-28 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 299 ISSN: 1522-1539 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-30 Completed Date: 2010-08-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H396-401 Citation Subset: IM |
Affiliation:
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Dept. of Physiology II, Nara Medical Univ. School of Medicine, 840 Shijo-cho, Kashihara, Nara 634.8521, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adrenergic beta-Antagonists
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pharmacology Animals Calpain / antagonists & inhibitors*, metabolism Carbamates / pharmacology* Cardiotonic Agents / pharmacology* Cysteine Proteinase Inhibitors / pharmacology* Energy Metabolism / drug effects* Excitation Contraction Coupling / drug effects Heart Ventricles / drug effects*, enzymology Male Oxygen Consumption / drug effects Perfusion Rats Rats, Wistar Receptors, Adrenergic, beta-1 / drug effects, metabolism Stroke Volume / drug effects Time Factors Ventricular Function, Left / drug effects* Ventricular Pressure / drug effects |
| Chemical | |
Reg. No./Substance:
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0/((1S)-1-((((1S)-1-benzyl-3-cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-methylbutyl)carbamic acid 5-methoxy-3-oxapentyl ester; 0/Adrb1 protein, rat; 0/Adrenergic beta-Antagonists; 0/Carbamates; 0/Cardiotonic Agents; 0/Cysteine Proteinase Inhibitors; 0/Receptors, Adrenergic, beta-1; EC 3.4.22.-/Calpain |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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