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The Cardio‐Protective Properties of Ncx‐6550, a Nitric Oxide Donating Pravastatin, in the Mouse
Author(s) -
DI FILIPPO CLARA,
MONOPOLI ANGELA,
ONGINI ENNIO,
PERRETTI MAURO,
D’AMICO MICHELE
Publication year - 2010
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/j.1549-8719.2010.00040.x
Subject(s) - pravastatin , nitric oxide , chemistry , pharmacology , microbiology and biotechnology , medicine , biochemistry , biology , organic chemistry , cholesterol
Please cite this paper as : Di Filippo, Monopoli, Ongini, Perretti and D’Amico (2010). The Cardio‐Protective Properties of Ncx‐6550, a Nitric Oxide Donating Pravastatin, in the Mouse. Microcirculation 17(6) , 417–426. Abstract Objective: Determine the cardio‐protective properties of a nitric oxide‐releasing pravastatin (Ncx‐6550), in comparison to pravastatin. Methods: A mouse model of myocardial infarct was used assessing tissue damage both at 2 and 24 hour post‐reperfusion, administering compounds both prophylactically and therapeutically. Results: Ncx‐6550 induced a significant dose‐dependent (2.24–22.4 μmol/kg i.p.) cardioprotection in the two hour reperfusion protocol. In vehicle‐treated mice, infarct size (expressed as fraction of area at risk; IS/AR) was 41.2 ± 1%, and it was reduced to 22.2 ± 0.9% and 32.6 ± 0.9% following 22.4 and 6.72 μmol/kg Ncx‐6550 ( p < 0.05). 22.4 μmol/kg Ncx‐6550 also increased cardiac levels of the enzyme heme oxygenase‐1. Treatment of mice with pravastatin induced significant reduction of myocardial injury only at 22.4 μmol/kg (IS/AR value: 33.7 ± 0.9%). In a 24 hour reperfusion protocol, Ncx‐6550 and pravastatin were tested only at 22.4 μmol/kg i.p. being given either one hour prior to ischemia (prophylactic protocol) or one hour into reperfusion (therapeutic protocol). With either treatment scheme, Ncx‐6550 produced higher cardioprotection compared to pravastatin, as reflected also by a reduction in the incidence of lethality as well as in circulating troponin I and interleukin‐1β levels. Conclusions: These results indicate Ncx‐6550 as a novel therapeutic agent with a potential for the treatment of myocardial infarct.