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Na+/H+ exchange inhibition with cariporide prevents alterations of coronary endothelial function in streptozotocin-induced diabetes.

Abstract : Hyperglycemia encountered during diabetes triggers abnormalities of vascular function associated with cell acidosis and calcium overload. The purpose of this study was to determine, whether Na+/H+ exchanger (NHE-1) inhibition by cariporide protects coronary cells against the deleterious effect of hyperglycemia in the rat. In vivo hyperglycemia was triggered by streptozotocin injection. One week after, the glycemia was checked and the control and diabetic animals were treated or not with cariporide (2.5 mg/kg/day) for two weeks. Glycemia was again estimated and the hearts were perfused according to the Langendorff mode at forced flow. The left ventricle developed pressure (LVDP) and heart rate (HR) were determined with a latex balloon inserted into the left ventricle. Coronary pressure was artificially increased to 130 mmHg by infusing a thromboxane A2 analogue (U46619). This allowed the evaluation of endothelium-dependent (EDD) and endothelium-independent (EID) dilatation through bolus injections of carbamoylcholin and sodium nitroprusside, respectively. Releases of lactate and pyruvate in the coronary effluents were also determined. Diabetes did not modified LVDP, but reduced HR (-15%). This was associated with a marked decrease in EDD (-56%) and EID (-30%), while the cytosolic redox potential (estimated as the lactate/pyruvate ratio) was reduced. NHE-1 inhibition restored EDD and the lactate/pyruvate ratio without improving EID and HR. The present findings indicate that NHE-1 exchanger inhibition by cariporide protects the coronary endothelium against the deleterious effects of hyperglycemia.
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https://www.hal.inserm.fr/inserm-00388539
Contributor : Sarah Hamant <>
Submitted on : Tuesday, May 26, 2009 - 10:32:28 PM
Last modification on : Thursday, November 19, 2020 - 3:54:28 PM

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Guillaume Vial, Hervé Dubouchaud, Karine Couturier, Martine Lanson, Xavier Leverve, et al.. Na+/H+ exchange inhibition with cariporide prevents alterations of coronary endothelial function in streptozotocin-induced diabetes.. Molecular and Cellular Biochemistry, Springer Verlag, 2008, 310 (1-2), pp.93-102. ⟨10.1007/s11010-007-9669-1⟩. ⟨inserm-00388539⟩

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