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Effects of sildenafil on nanostructural and nanomechanical changes in mitochondria in an ischaemia‐reperfusion rat model
Author(s) -
Lee Kyung Hye,
Kwon Sung Jin,
Woo JongShin,
Lee GiJa,
Lee SoRa,
Jang HyunHee,
Kim Hyun Soo,
Kim Jung Wook,
Park Hun Kuk,
Cho Kyu Seok,
Kim Weon
Publication year - 2014
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12290
Subject(s) - sildenafil , cardioprotection , mitochondrion , ischemia , chemistry , reperfusion injury , in vivo , medicine , pharmacology , endocrinology , anesthesia , biology , biochemistry , microbiology and biotechnology
Summary Sildenafil exerts cardioprotective effects by activating the opening of mitochondrial ATP ‐sensitive potassium channels to attenuate ischaemia–reperfusion ( IR ) injury. In the present study, we used atomic force microscopy ( AFM ) to investigate changes in mitochondrial morphology and properties to assess sildenafil‐mediated cardioprotection in a rat myocardial infarction model. To investigate the cardioprotective effects of sildenafil, we used an in vivo Sprague‐Dawley rat model of IR . Rats were randomly divided into three groups: (i) sham‐operated rats (control; n = 5); (ii) IR ‐injured rats treated with vehicle (normal saline; IR ; n = 10); and (iii) IR ‐injured rats treated with 0.75 mg/kg, i.p., sildenafil ( IR + Sil; n = 10). Morphological and mechanical changes to mitochondria were analysed by AFM . Infarct areas were significantly reduced in sildenafil‐treated rats (7.8 ± 3.9% vs 20.4 ± 7.0% in the sildenafil‐treated and untreated IR groups, respectively; relative reduction 62%; P < 0.001). Analysis of mitochondria by AFM showed that IR injury significantly increased the areas of isolated mitochondria compared with control (24 150 ± 18 289 vs 1495 ± 1139 nm 2 , respectively; P < 0.001), indicative of mitochondrial swelling. Pretreatment with sildenafil before IR injury reduced the mitochondrial areas (7428 ± 3682 nm 2 ; P < 0.001; relative reduction 69.2% compared with the IR group) and ameliorated the adhesion force of mitochondrial surfaces. Together, these results suggest that sildenafil has cardioprotective effects against IR injury in a rat model by improving the morphological and mechanical characteristics of mitochondria.