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sGCα1β1 attenuates cardiac dysfunction and mortality in murine inflammatory shock models
BMC Pharmacology volume 9, Article number: P5 (2009)
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 mice deficient in sGCα1 (sGCα1-/-mice) to unequivocally determine the role of sGCα1β1 in the development of cardiac dysfunction and death associated with two models of inflammatory shock: endotoxin-induced and TNF-induced shock.
At baseline, echocardiographic assessment and invasive hemodynamic measurements of left ventricular (LV) dimensions and function did not differ between WT and sGCα1-/-mice on the C57BL/6 background (sGCα1-/-B6 mice). Fourteen hours after a challenge with endotoxin, cardiac dysfunction was more pronounced in sGCα1-/-B6 mice than in WT mice, as assessed using echocardiographic and hemodynamic indices of LV function. Similarly, Ca2+ handling and cell shortening were impaired to a greater extent in cardiac myocytes isolated from sGCα1-/-B6 mice than in those from WT mice after a challenge with endotoxin. Importantly, morbidity and mortality associated with inflammatory shock induced either by endotoxin or TNF were increased in sGCα1-/-B6 mice as compared to WT mice.
Together, these findings suggest that cGMP generated by sGCα1β1 protects against cardiac dysfunction and mortality in murine models of inflammatory shock.
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Buys, E.S., Cauwels, A., Raher, M.J. et al. sGCα1β1 attenuates cardiac dysfunction and mortality in murine inflammatory shock models. BMC Pharmacol 9, P5 (2009). https://doi.org/10.1186/1471-2210-9-S1-P5
- Murine Model
- Left Ventricular Function
- Cardiac Myocytes
- Cardiac Dysfunction
- Guanylate Cyclase