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Atorvastatin prevents sepsis-induced downregulation of myocardial β1-adrenoceptors and decreased cAMP response in mice

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Title Atorvastatin prevents sepsis-induced downregulation of myocardial β1-adrenoceptors and decreased cAMP response in mice
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Creator Thangamalai R, Kandasamy K, Sukumarn SV, Reddy N, Singh V, Choudhury S, Parida S, Singh TU, Boobalan R, Mishra SK
 
Subject "b1-adrenoceptor, catecholamines, GRK2, heart, sepsis, statin
 
Description Not Available
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 postYreceptor signaling in a mouse model of sepsis (cecal ligation and puncture [CLP]). After 20 T
2 h of surgery, hearts were isolated for the measurement of left ventricular functions (left ventricular developed pressure, dp/
dtmax and dp/dtmin) using Langendorff setup. Western blot was used to determine "1-AR and G proteinYcoupled 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 T 0.53 vs. ATR 100.24 T 1.64 mmHg), dp/dtmax (CLP 3,742 T 71 vs. ATR 4,291 T 88 mmHg/s), and dp/dtmin
(CLP j1,010 T 24 vs. ATR j1,346 T 84 mmHg/s). Associated with functional impairments, sepsis decreased both myocardial
"1-AR protein and mRNA expressions by 52% T 9% and 62% T 7%, respectively. However, ATR treatment of CLP mice (ATR)
preserved "1-AR protein (96% T 11%) and mRNA (88% T 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 T 0.27 vs. ATR 6.30 T 0.67 pmol/mg protein), but also prevented its refractoriness to dobutamine stimulation
(CLP 1.72 T 0.27 vs. ATR 10.83 T 1.37 pmol/mg protein). Atorvastatin also inhibited sepsis-induced increase in cardiac G
proteinYcoupled receptor kinase 2 protein expression (CLP 1.73 T 0.18-fold vs. ATR 1.10 T 0.18-fold), protein kinase A
activity (CLP 1.12 T 0.14 vs. ATR 0.66 T 0.08 U/mg protein) and plasma catecholamines (CLP 138 T 22 vs. ATR 59 T 2 pg/mL).
In conclusion, ATR seems to improve left ventricular functions in vitro through the preservation of "1-AR signaling in sepsis
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Date 2023-06-05T09:00:08Z
2023-06-05T09:00:08Z
2014-01-08
 
Type Article
 
Identifier Thangamalai R, Kandasamy K, Sukumarn SV, Reddy N, Singh V, Choudhury S, Parida S, Singh TU, Boobalan R, Mishra SK. Atorvastatin prevents sepsis-induced downregulation of myocardial β1-adrenoceptors and decreased cAMP response in mice. Shock. 2014 May;41(5):406-12. doi: 10.1097/SHK.0000000000000138. PMID: 24430540.
Not Available
http://krishi.icar.gov.in/jspui/handle/123456789/78031
 
Language English
 
Relation Not Available;
 
Publisher Lippincott Williams & Wilkins