β3-Adrenergic receptor antagonism improves cardiac and vascular functions but did not modulate survival in a murine resuscitated septic shock model
Abstract Background Recent findings suggest that β3-adrenergic receptors (β3-AR) could play a role in the hemodynamic regulation, but their function in septic shock remains unclear. This study investigates the modulation of β3-AR in an experimental murine model of resuscitated septic shock on in viv...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SpringerOpen
2024-12-01
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| Series: | Intensive Care Medicine Experimental |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40635-024-00705-9 |
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| Summary: | Abstract Background Recent findings suggest that β3-adrenergic receptors (β3-AR) could play a role in the hemodynamic regulation, but their function in septic shock remains unclear. This study investigates the modulation of β3-AR in an experimental murine model of resuscitated septic shock on in vivo hemodynamic, ex vivo vasoreactivity, inflammation and survival. Method Wild-type mice were used, undergoing cecal ligation and puncture (CLP) to induce septic shock, with SHAM as controls. Mice were treated with β3-AR agonist or antagonist three hours post-CLP, followed by resuscitation with fluids and antibiotics. Hemodynamic parameters were measured at 18 h following the surgery, and the expression of β-ARs in heart and aorta was assessed via immunostaining and western blot. Vascular reactivity was studied using myography, and inflammatory markers were analyzed through PCR and western blots. A 5-day survival study was conducted, documenting clinical severity scores and survival rates. Results β3-AR was expressed in both endothelial and myocardial cells in healthy and septic mice. During septic shock model, β3-AR density on endothelial cells increased post-CLP, while β1- and β2-AR decreased or remained constant. β3-AR antagonist treatment improved hemodynamic parameters, increasing mean arterial pressure and cardiac index, unlike the agonist. Vascular reactivity to phenylephrine was enhanced in aortic rings from both β3-AR agonist and antagonist-treated mice. However, no significant differences in inducible NO synthase expression were observed among treated groups. Despite improved hemodynamic parameters with β3-AR antagonist treatment, survival rates in treated groups remained similar to CLP group. Conclusions In an experimental murine model of resuscitated septic shock, β3-AR is resistant to desensitization and its inhibition improves cardiac and vascular function without affecting the short-term survival. |
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| ISSN: | 2197-425X |