TY - JOUR
T1 - Interaction between paracrine tumor necrosis factor-alpha and paracrine angiotensin II during myocardial ischemia
AU - Frolkis, Inna
AU - Gurevitch, Jacob
AU - Yuhas, Yael
AU - Iaina, Adrian
AU - Wollman, Yoram
AU - Chernichovski, Tamara
AU - Paz, Yosef
AU - Matsa, Menachem
AU - Pevni, Dimitri
AU - Kramer, Amir
AU - Shapira, Itzhak
AU - Mohr, Rephael
N1 - Funding Information:
This study was supported by the Research Fund of the Department of Thoracic and Cardiovascular Surgery, Sourasky Tel Aviv Medical Center.
PY - 2001/1/27
Y1 - 2001/1/27
N2 - OBJECTIVES: The purpose of this study was to explore interactions between paracrine angiotensin II (Ang-II) and tumor necrosis factor-alpha (TNF-alpha) during myocardial ischemia. BACKGROUND: Ischemic myocardium releases significant amounts of TNF-alpha. This paracrine release correlated with postischemic myocardial injury. Other studies showed myocardial protection obtained by the use of angiotensin-converting enzyme inhibitors (i.e., captopril) and the Ang-II type 1 receptor antagonist losartan after ischemia. The possibility that these agents decrease TNF-alpha synthesis has not yet been investigated. METHODS: Using the modified Langendorff model, isolated rat hearts underwent either 90 min of nonischemic perfusion (control group) or 1 h of global cardioplegic ischemia. In both groups, either captopril (360 μmol/liter) or losartan (182.2 μmol/liter) was added before ischemia. The hearts were assayed for messenger ribonucleic acid (mRNA) expression and effluent TNF-alpha levels. In addition, cardiac myocytes were incubated in cell culture with Ang-II. RESULTS: After ischemia, TNF-alpha mRNA expression intensified from 0.63 ± 0.06 (control group) to 0.92 ± 0.12 (p < 0.03), and effluent TNF-alpha levels were 711 ± 154 pg/ml. The TNF-alpha mRNA expression declined to 0.46 ± 0.07 (p < 0.01) and 0.65 ± 0.08 (p < 0.02) in captopril- and losartan-treated hearts, respectively. Effluent TNF-alpha was below detectable levels. Concentrations of TNF-alpha in supernatants of incubated cardiac myocytes treated with 10 and 50 nmol/liter of Ang-II were 206.0 ± 47.0 pg/ml and 810 ± 130 pg/ml, respectively (p < 0.004). When pretreated with 700 μmol/liter of losartan, TNF-alpha was below detectable levels. CONCLUSIONS: This study presents an original explanation for previously reported myocardial protection after ischemia, obtained by the use of captopril and losartan. These drugs reduce TNF-alpha synthesis, providing strong evidence of active interactions between paracrine TNF-alpha and Ang-II in the evolution of the ischemic cascade.
AB - OBJECTIVES: The purpose of this study was to explore interactions between paracrine angiotensin II (Ang-II) and tumor necrosis factor-alpha (TNF-alpha) during myocardial ischemia. BACKGROUND: Ischemic myocardium releases significant amounts of TNF-alpha. This paracrine release correlated with postischemic myocardial injury. Other studies showed myocardial protection obtained by the use of angiotensin-converting enzyme inhibitors (i.e., captopril) and the Ang-II type 1 receptor antagonist losartan after ischemia. The possibility that these agents decrease TNF-alpha synthesis has not yet been investigated. METHODS: Using the modified Langendorff model, isolated rat hearts underwent either 90 min of nonischemic perfusion (control group) or 1 h of global cardioplegic ischemia. In both groups, either captopril (360 μmol/liter) or losartan (182.2 μmol/liter) was added before ischemia. The hearts were assayed for messenger ribonucleic acid (mRNA) expression and effluent TNF-alpha levels. In addition, cardiac myocytes were incubated in cell culture with Ang-II. RESULTS: After ischemia, TNF-alpha mRNA expression intensified from 0.63 ± 0.06 (control group) to 0.92 ± 0.12 (p < 0.03), and effluent TNF-alpha levels were 711 ± 154 pg/ml. The TNF-alpha mRNA expression declined to 0.46 ± 0.07 (p < 0.01) and 0.65 ± 0.08 (p < 0.02) in captopril- and losartan-treated hearts, respectively. Effluent TNF-alpha was below detectable levels. Concentrations of TNF-alpha in supernatants of incubated cardiac myocytes treated with 10 and 50 nmol/liter of Ang-II were 206.0 ± 47.0 pg/ml and 810 ± 130 pg/ml, respectively (p < 0.004). When pretreated with 700 μmol/liter of losartan, TNF-alpha was below detectable levels. CONCLUSIONS: This study presents an original explanation for previously reported myocardial protection after ischemia, obtained by the use of captopril and losartan. These drugs reduce TNF-alpha synthesis, providing strong evidence of active interactions between paracrine TNF-alpha and Ang-II in the evolution of the ischemic cascade.
UR - http://www.scopus.com/inward/record.url?scp=0035174554&partnerID=8YFLogxK
U2 - 10.1016/S0735-1097(00)01055-X
DO - 10.1016/S0735-1097(00)01055-X
M3 - Article
AN - SCOPUS:0035174554
SN - 0735-1097
VL - 37
SP - 316
EP - 322
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 1
ER -