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sGCα1β1 attenuates cardiac dysfunction and mortality in murine inflammatory shock models

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Abstract
Altered cGMP signaling has been implicated in myocardial depression, morbidity, and mortality associated with sepsis. Previous studies, using inhibitors of soluble guanylate cyclase (sGC), suggested that cGMP generated by sGC contributed to the cardiac dysfunction and mortality associated with sepsis. We used sGC alpha(1)-deficient (sGC alpha(-/-)(1)) mice to unequivocally determine the role of sGC alpha(1)beta(1) in the development of cardiac dysfunction and death associated with two models of inflammatory shock: endotoxin-and TNF-induced shock. At baseline, echocardiographic assessment and invasive hemodynamic measurements of left ventricular (LV) dimensions and function did not differ between wild-type (WT) mice and sGC alpha(-/-)(1) mice on the C57BL/6 background (sGC alpha(-/-B6)(1) mice). At 14 h after endotoxin challenge, cardiac dysfunction was more pronounced in sGC alpha(-/-B6)(1) than WT mice, as assessed using echocardiographic and hemodynamic indexes of LV function. Similarly, Ca2+ handling and cell shortening were impaired to a greater extent in cardiomyocytes isolated from sGC alpha(-/-B6)(1) than WT mice after endotoxin challenge. Importantly, morbidity and mortality associated with inflammatory shock induced by endotoxin or TNF were increased in sGC alpha(-/-B6)(1) compared with WT mice. Together, these findings suggest that cGMP generated by sGC alpha(1)beta(1) protects against cardiac dysfunction and mortality in murine inflammatory shock models.
Keywords
METHYLENE-BLUE, MYOCARDIAL DYSFUNCTION, CGMP, PRESSURE-OVERLOAD, nitric oxide, mice, sepsis, left ventricular function, soluble guanylate cyclase, ENOS-DERIVED NO, HUMAN SEPTIC SHOCK, NITRIC-OXIDE SYNTHASE, SENSITIVE GUANYLYL CYCLASE, SEVERE SEPSIS, MICE LACKING

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Citation

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Chicago
Buys, Emmanuel S, Anje Cauwels, Michael J Raher, Jonathan J Passeri, Ion Hobai, Sharon M Cawley, Kristen M Rauwerdink, et al. 2009. “sGCα1β1 Attenuates Cardiac Dysfunction and Mortality in Murine Inflammatory Shock Models.” American Journal of Physiology-heart and Circulatory Physiology 297 (2): H654–H663.
APA
Buys, E. S., Cauwels, A., Raher, M. J., Passeri, J. J., Hobai, I., Cawley, S. M., Rauwerdink, K. M., et al. (2009). sGCα1β1 attenuates cardiac dysfunction and mortality in murine inflammatory shock models. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 297(2), H654–H663.
Vancouver
1.
Buys ES, Cauwels A, Raher MJ, Passeri JJ, Hobai I, Cawley SM, et al. sGCα1β1 attenuates cardiac dysfunction and mortality in murine inflammatory shock models. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY. 2009;297(2):H654–H663.
MLA
Buys, Emmanuel S, Anje Cauwels, Michael J Raher, et al. “sGCα1β1 Attenuates Cardiac Dysfunction and Mortality in Murine Inflammatory Shock Models.” AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY 297.2 (2009): H654–H663. Print.
@article{787188,
  abstract     = {Altered cGMP signaling has been implicated in myocardial depression, morbidity, and mortality associated with sepsis. Previous studies, using inhibitors of soluble guanylate cyclase (sGC), suggested that cGMP generated by sGC contributed to the cardiac dysfunction and mortality associated with sepsis. We used sGC alpha(1)-deficient (sGC alpha(-/-)(1)) mice to unequivocally determine the role of sGC alpha(1)beta(1) in the development of cardiac dysfunction and death associated with two models of inflammatory shock: endotoxin-and TNF-induced shock. At baseline, echocardiographic assessment and invasive hemodynamic measurements of left ventricular (LV) dimensions and function did not differ between wild-type (WT) mice and sGC alpha(-/-)(1) mice on the C57BL/6 background (sGC alpha(-/-B6)(1) mice). At 14 h after endotoxin challenge, cardiac dysfunction was more pronounced in sGC alpha(-/-B6)(1) than WT mice, as assessed using echocardiographic and hemodynamic indexes of LV function. Similarly, Ca2+ handling and cell shortening were impaired to a greater extent in cardiomyocytes isolated from sGC alpha(-/-B6)(1) than WT mice after endotoxin challenge. Importantly, morbidity and mortality associated with inflammatory shock induced by endotoxin or TNF were increased in sGC alpha(-/-B6)(1) compared with WT mice. Together, these findings suggest that cGMP generated by sGC alpha(1)beta(1) protects against cardiac dysfunction and mortality in murine inflammatory shock models.},
  author       = {Buys, Emmanuel S and Cauwels, Anje and Raher, Michael J and Passeri, Jonathan J and Hobai, Ion and Cawley, Sharon M and Rauwerdink, Kristen M and Thibault, H{\'e}l{\`e}ne  and Sips, Patrick and Thoonen, Robrecht and Scherrer-Crosbie, Marielle and Ichinose, Fumito and Brouckaert, Peter and Bloch, Kenneth D},
  issn         = {0363-6135},
  journal      = {AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY},
  language     = {eng},
  number       = {2},
  pages        = {H654--H663},
  title        = {sGC\ensuremath{\alpha}1\ensuremath{\beta}1 attenuates cardiac dysfunction and mortality in murine inflammatory shock models},
  url          = {http://dx.doi.org/10.1152/ajpheart.00367.2009},
  volume       = {297},
  year         = {2009},
}

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