Detail of "159138-80-4"

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Cariporide preserves mitochondrial proton gradient and delays ATP depletion in cardiomyocytes during ischemic conditions

Cariporide preserves mitochondrial proton gradient and delays ATP depletion in cardiomyocytes during ischemic conditions. Ruiz-Meana, Marisol; Garcia-Dorado, David; Pina, Pilar; Inserte, Javier; Agullo, Luis; Soler-Soler, Jordi (Cardiology Department, Hospital Vall d'Hebron, Barcelona 08035, Spain). American Journal of Physiology, 285(3, Pt. 2), H999-H1006 (English) 2003 American Physiological Society. CODEN: AJPHAP. ISSN: 0002-9513. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The mechanism by which inhibition of Na+/H+ exchanger (NHE) reduces cell death in ischemic-reperfused myocardium remains controversial. This study investigated whether cariporide could inhibit mitochondrial NHE during ischemia, delaying H+ gradient dissipation and ATP exhaustion. Mouse cardiac myocytes (HL-1) were submitted to 1 h of simulated ischemia (SI) with NaCN/deoxyglucose (pH 6.4), with or without 7 mM cariporide, and mitochondrial concn. of Ca2+ (Rhod-2), 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) and the charge difference across the mitochondrial membrane potential (DYm, JC-1) were assessed. ATP content was measured by bioluminescence and mitochondrial swelling by spectrophotometry in isolated mitochondria. Cariporide significantly attenuated the acidification of the mitochondrial matrix induced by SI without modifying DYm decay, and this effect was assocd. to a delayed ATP exhaustion and increased mitochondrial Ca2+ load. These effects were reproduced in sarcolemma-permeabilized cells exposed to SI. In these cells, cariporide markedly attenuated the fall in mitochondrial pH induced by removal of Na+ from the medium. In isolated mitochondria, cariporide significantly reduced the rate and magnitude of passive matrix swelling induced by Na+ acetate. In isolated rat hearts submitted to 40-min ischemia at different temps. (35.5°, 37°, or 38. 56-65-5 and 159138-80-4 which are cas registry numbers of substances are two of reagents here.5°) pretreatment with cariporide limited ATP depletion during the first 10 min of ischemia and cell death (lactate dehydrogenase release) during reperfusion. These effects were mimicked when a similar ATP preservation was achieved by hypothermia and were abolished when the sparing effect of cariporide on ATP was suppressed by hyperthermia. We conclude that cariporide acts at the mitochondrial level, delaying mitochondrial matrix acidification and delaying ATP exhaustion during ischemia. These effects can contribute to reduce cell death secondary to ischemia-reperfusion. .

Cardioprotection with cariporide, a sodium-proton exchanger inhibitor, after prolonged ischemia and reperfusion in senescent rats

Cardioprotection with cariporide, a sodium-proton exchanger inhibitor, after prolonged ischemia and reperfusion in senescent rats. Besse, Sophie; Tanguy, Stephane; Boucher, Francois; Le Page, Christine; Rozenberg, Sandrine; Riou, Bruno; de Leiris, Joel; Swynghedauw, Bernard (Laboratoire Nutrition, Vieillissement et Maladies Cardiovasculaires, Universite Joseph Fourier, La Tronche, Fr.). Experimental Gerontology, 39(9), 1307-1314 (English) 2004 Elsevier B.V. CODEN: EXGEAB. ISSN: 0531-5565. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) This study investigated the effects of cariporide, an inhibitor of sodium-proton exchanger (NHE), during myocardial ischemia and reperfusion in senescence. Isolated Langendorff perfused hearts from 4 (adult) and 24 (senescent) month old male Wistar rats were submitted to prolonged low-flow ischemia (LFI) at 15% of initial coronary flow (180 min) or to 45 min of LFI (15% of initial coronary flow) followed by 30 min of reperfusion, without or with cariporide (10-6 M). In senescent hearts, but not in adults, treatment with cariporide during prolonged LFI attenuated the elevation of coronary resistances (578±84 vs 1020±129% of baseline value after 180 min, P<0.05) and delayed the decrease in active tension (35.6±5.1 vs 22.2±3.4% of baseline value after 60 min; P<0.05). During reperfusion following LFI, the coronary flow impairment was more pronounced in senescents than in adults (48.4±9.4 and 75.3±4.9% of baseline value, resp.; P<0.05) but was fully prevented in senescent hearts by cariporide treatment (95.6±17.0% of baseline value; P<0.05 vs untreated group). This beneficial effect of cariporide on coronary tone was assocd. with an improvement of active and resting tensions and lower LDH release. Such functional protective effects of cariporide suggest an operative NHE during LFI at both coronary and myocardial levels in senescent heart. In addn., cariporide-assocd. 9001-60-9 and 159138-80-4 are just another two chemicals used in this study. improvement of post-ischemic recovery of coronary and contractile function as well as the limitation of cellular injury suggests a major role of calcium overload via NHE activation during reperfusion of senescent ischemic heart. .