IMR Press / FBL / Volume 23 / Issue 2 / DOI: 10.2741/4592

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

L-NAME improves doxycycline and ML-7 cardioprotection from oxidative stress

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1 Department of Clinical Chemistry, Wroclaw Medical University, Wroclaw, Poland
2 Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada
3 Department and Clinic of Cardiology, Wroclaw Medical University, Wroclaw, Poland
4 Department of Emergency Medicine, Wroclaw Medical University, Wroclaw, Poland
Front. Biosci. (Landmark Ed) 2018, 23(2), 298–309; https://doi.org/10.2741/4592
Published: 1 January 2018
(This article belongs to the Special Issue Advances in cardiometabolic diseases and related complications)
Abstract

Matrix metalloproteinase-2 (MMP-2) mediated degradation of myosin light chain 1 (MLC1) and troponin I (TnI) contributes to myocardial ischemia/reperfusion (I/R) injury. Modifications of MLC1 triggered by oxidative stress are mediated by myosin light chain kinase (MLCK), nitric oxide synthase (NOS), and MMP-2. Previous studies have shown that inhibiting both MLCK and MMP-2 protects against I/R injury. Here, we hypothesized that the addition of NOS inhibitor (L-NAME) at subprotective concentration to the mixture of subprotective concentrations of ML-7 and doxycycline (Doxy), will increase a synergistic cardioprotection of Doxy and ML-7 during I/R. Isolated rat hearts were subjected to global ischemia without or with administration of the mixture of inhibitors. Markers of I/R injury were measured in hearts and coronary effluents. Addition of L-NAME to the mixture of Doxy and ML-7 led to full recovery of heart contractility in comparison to combination of Doxy and ML-7. Improved heart contractility was associated with reduced degradation of TnI and MLC1. The combined administration of NOS, MMP-2 and MLCK inhibitors provides a novel strategy to protect heart from I/R injury.

Keywords
Ischemia
Reperfusion
Isolated rat heart
Doxycycline
ML-7
L-NAME
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