Abstract
BackgroundMyocardial infarction (MI) is considered a public health problem. According to the World Health Organization, MI is a leading cause of death and comorbidities worldwide. Activation of the alpha 1A adrenergic receptor is a contributing factor to the development of MI. Tamsulosin, an alpha 1A adrenergic blocker, has gained wide popularity as a medication for the treatment of benign prostatic hyperplasia. Limited evidence from previous studies has revealed the potential cardioprotective effects of tamsulosin, as its inhibitory effect on the alpha 1A adrenoceptor protects the heart by acting on the smooth muscle of blood vessels, which results in hypotension; however, its effect on the infarcted heart is still unclear. The mechanisms of the expected cardioprotective effects mediated by tamsulosin are not yet understood. Transforming growth factor-beta (TGF-beta), a mediator of fibrosis, is considered an attractive therapeutic target for remodeling after MI. The role of alpha 1A adrenoceptor inhibition or its relationships with integrin-linked kinase (ILK) and TGF-beta/small mothers against decapentaplegic (Smad) signaling pathways in attenuating MI are unclear. The present study was designed to investigate whether tamsulosin attenuates MI by modulating an ILK-related TGF-beta/Smad pathway.MethodsTwenty-four adult male Wistar rats were randomly divided into 4 groups: control, ISO, TAM, and ISO + TAM. ISO (150 mg/kg, intraperitoneally) was injected on Days 20 and 21 to induce MI. Tamsulosin (0.8 mg/kg, orally) was administered for 21 days, prior to ISO injection for 2 consecutive days. Heart-to-body weight ratios and cardiac and fibrotic biomarker levels were subsequently determined. ILK, TGF-beta 1, p-Smad2/3, and collagen III protein expression levels were determined using biomolecular methods.ResultsTamsulosin significantly attenuated the relative heart-to-body weight index (p < 0.5) and creatine kinase-MB level (p < 0.01) compared with those in the ISO control group. While ISO resulted in superoxide anion production and enhanced oxidative damage, tamsulosin significantly prevented this damage through antioxidant defense mechanisms, increasing glutathione and superoxide dismutase levels (p < 0.05) and decreasing lipid peroxide oxidation levels (p < 0.01). The present data revealed that tamsulosin reduced TGF-beta/p-Smad2/3 expression and enhanced ILK expression.ConclusionTamsulosin may exert a cardioprotective effect by modulating the ILK-related TGF-beta/Smad signaling pathway. Thus, tamsulosin may be a useful therapeutic approach for preventing MI.