| Autor: |
Thangamalai, Ramasamy, Kandasamy, Kannan, Sukumarn, Susanth V., Reddy, Narasimha, Singh, Vishakha, Choudhury, Soumen, Parida, Subhashree, Singh, Thakur Uttam, Boobalan, Raja, Mishra, Santosh Kumar |
| Zdroj: |
Shock; May 2014, Vol. 41 Issue: 5 p406-412, 7p |
| Abstrakt: |
Impaired cardiac -adrenoceptor signaling is an important cause of sepsis-induced myocardial depression in man and experimental animals. We examined the effect of atorvastatin (ATR) pretreatment on myocardial 1-adrenoceptor (1-AR) expressions and post–receptor signaling in a mouse model of sepsis (cecal ligation and puncture CLP). After 20 ± 2 h of surgery, hearts were isolated for the measurement of left ventricular functions (left ventricular developed pressure, dpdtmaxand dpdtmin) using Langendorff setup. Western blot was used to determine 1-AR and G protein–coupled receptor kinase 2 protein expressions. Real-time polymerase chain reaction was done to determine 1-AR mRNA expression. Atorvastatin prevented sepsis-induced decrease in left ventricular functions, such as left ventricular developed pressure (CLP 75.90 ± 0.53 vs. ATR 100.24 ± 1.64 mmHg), dpdtmax(CLP 3,742 ± 71 vs. ATR 4,291 ± 88 mmHgs), and dpdtmin(CLP −1,010 ± 24 vs. ATR −1,346 ± 84 mmHgs). Associated with functional impairments, sepsis decreased both myocardial 1-AR protein and mRNA expressions by 52 ± 9 and 62 ± 7, respectively. However, ATR treatment of CLP mice (ATR) preserved 1-AR protein (96 ± 11) and mRNA (88 ± 14) expressions comparable to sham-operated level. Furthermore, it not only attenuated sepsis-induced decrease in basal cardiac adenosine 3′,5′-cyclic monophosphate content (CLP 1.30 ± 0.27 vs. ATR 6.30 ± 0.67 pmolmg protein), but also prevented its refractoriness to dobutamine stimulation (CLP 1.72 ± 0.27 vs. ATR 10.83 ± 1.37 pmolmg protein). Atorvastatin also inhibited sepsis-induced increase in cardiac G protein–coupled receptor kinase 2 protein expression (CLP 1.73 ± 0.18-fold vs. ATR 1.10 ± 0.18-fold), protein kinase A activity (CLP 1.12 ± 0.14 vs. ATR 0.66 ± 0.08 Umg protein) and plasma catecholamines (CLP 138 ± 22 vs. ATR 59 ± 2 pgmL). In conclusion, ATR seems to improve left ventricular functions in vitrothrough the preservation of 1-AR signaling in sepsis. |
| Databáze: |
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