| Autor: |
Pitcher, Jeffrey M., Wang, Meijing, Tsai, Ben M., Kher, Ajay, Nelson, Nicholas T., Meldrum, Daniel R. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Regulatory, Integrative & Comparative Physiology; Jan2006, Vol. 290, p27-33, 6p, 8 Diagrams |
| Abstrakt: |
Myocardial endotoxin tolerance may be induced in both males and females; however, it remains unknown whether there are mechanistic and threshold differences between the sexes. We hypothesized that endogenous estrogen mediates a higher threshold for endotoxin (ETX)-induced protection in females. Adult proestrus and ovariectomized (OVX) female rats were preconditioned (PC) with intraperitoneal injections of 125 (PC+125) or 500 (PC+500) μg/kg Salmonella typhimurium LPS (ETX) or normal saline (PC-). Twenty-four hours later, injury dose ETX (500 μg/kg) was injected. After 6 h, myocardial function was measured via Langendorff. p38 MAPK and JNK activation and TNF-α, IL-1, and IL-6 expression were evaluated. ETX injury significantly decreased left ventricular developed pressure in PC-groups vs. controls. PC + 500 regimen protected against ETX injury, resulting in normal cardiac function. PC + 125 regimen protected OVX but not proestrus females, which had diminished myocardial function. Activated JNK and TNF-α increased in PC- but were diminished in PC + 500 animals, importantly, activated JNK and TNF increased in PC + 125 proestrus females, whereas PC + 125 OVX females displayed decreases in these molecules. There were no differences in p38 MAPK activation or expression of IL-1 or IL-6. These results demonstrate that proestrus females require a higher stimulus (PC+500) to achieve myocardial protection against ETX injury. Removal of endogenous estrogen (OVX) lowered the preconditioning threshold (PC + 125), resulting in protection after lesser injury. Additionally, myocardial JNK and TNF expression was decreased in OVX PC + 125 females, which correlated with myocardial function differences. Therefore, we conclude that endogenous estrogen mediates a higher threshold for ETX tolerance in female myocardium. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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