[Metalloproteinase activity in myocardium of rats exposed to endotoxin and its inhibition with doxycycline].
BACKGROUND
The ventricular dysfunction of endotoxic shock could be secondary to the activity of myocardial metalloproteinases that degrade collagenous matrix. Metalloproteinase activity can be inhibited with doxycycline in some tissues.


OBJECTIVE
To study if the effect of endotoxemia on myocardial metalloproteinase activity can be inhibited with doxycycline.


METHODS
Left ventricular metalloproteinase activity was studied in four groups of rats. Group 1 received intraperitoneal dextrose in water, group 2 received 8 mg/kg intraperitoneal E coli endotoxin, group 3 received 60 mg/kg/day doxycycline for three days and group 4 received doxycycline and E coli endotoxin. Enzymatic activity was measured by Western Blot and zymography.


RESULTS
Zymography showed a higher metalloproteinase 2 (49%) and 9 (100%) activity in rats treated with endotoxin, when compared with control rats. In group 4, doxycycline reduced the activity of metalloproteinases 2 and 9 by 71% and 63% respectively, as compared with group 3. Western blot showed a 50% increase in the expression of metalloproteinase 1 in rats treated with endotoxin, that was reduced by 64% with the use of doxycycline.


CONCLUSIONS
Endotoxin administration increases myocardial metalloproteinases and doxycyclin inhibits this activation. Therefore, doxycyclin could reduce the degradation of myocardial fibrillar collagen and ventricular dysfunction of endotoxic shock.
Ruiz
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S
Departamento de Enfermedades Cardiovasculares, Facultad de Medicina Pontificia Universidad Católica de Chile.
Morales
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D
Guarda
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E
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003094:Collagen / Q000494:pharmacology*; D004318:Doxycycline / Q000494:pharmacology*; D019446:Endotoxemia / Q000188:drug therapy*; D004926:Escherichia coli / Q000187:drug effects*; D008297:Male; D008666:Metalloendopeptidases / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000188:drug therapy
D000900:Anti-Bacterial Agents; D003094:Collagen; D008666:Metalloendopeptidases; D004318:Doxycycline
Actividad de las metaloproteinasas en el miocardio de ratas sometidas a endotoxina y su inhibición con doxiciclina.