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...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SpringerOpen
2024-12-01
|
| Series: | Intensive Care Medicine Experimental |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40635-024-00705-9 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850101853115645952 |
|---|---|
| author | Eugénie Hagimont Marc-Damien Lourenco-Rodrigues Benjamin-Glenn Chousterman Frances Yen-Potin Manon Durand Antoine Kimmoun |
| author_facet | Eugénie Hagimont Marc-Damien Lourenco-Rodrigues Benjamin-Glenn Chousterman Frances Yen-Potin Manon Durand Antoine Kimmoun |
| author_sort | Eugénie Hagimont |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5abfd3d8eefe4890aefae46e0053e42d |
| institution | DOAJ |
| issn | 2197-425X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Intensive Care Medicine Experimental |
| spelling | doaj-art-5abfd3d8eefe4890aefae46e0053e42d2025-08-20T02:39:54ZengSpringerOpenIntensive Care Medicine Experimental2197-425X2024-12-0112111110.1186/s40635-024-00705-9β3-Adrenergic receptor antagonism improves cardiac and vascular functions but did not modulate survival in a murine resuscitated septic shock modelEugénie Hagimont0Marc-Damien Lourenco-Rodrigues1Benjamin-Glenn Chousterman2Frances Yen-Potin3Manon Durand4Antoine Kimmoun5Inserm U1116, DCAC, Université de LorraineInserm U1116, DCAC, Université de LorraineAPHP, CHU Lariboisière, Département d’anesthésiologie et Réanimation, Inserm, MASCOT Paris, Université Paris CitéInserm U1116, DCAC, Université de LorraineInserm U1116, DCAC, Université de LorraineInserm U1116, DCAC, Université de LorraineAbstract 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.https://doi.org/10.1186/s40635-024-00705-9Septic shockReceptorBeta-3AdrenergicVascular reactivity |
| spellingShingle | Eugénie Hagimont Marc-Damien Lourenco-Rodrigues Benjamin-Glenn Chousterman Frances Yen-Potin Manon Durand Antoine Kimmoun β3-Adrenergic receptor antagonism improves cardiac and vascular functions but did not modulate survival in a murine resuscitated septic shock model Intensive Care Medicine Experimental Septic shock Receptor Beta-3 Adrenergic Vascular reactivity |
| title | β3-Adrenergic receptor antagonism improves cardiac and vascular functions but did not modulate survival in a murine resuscitated septic shock model |
| title_full | β3-Adrenergic receptor antagonism improves cardiac and vascular functions but did not modulate survival in a murine resuscitated septic shock model |
| title_fullStr | β3-Adrenergic receptor antagonism improves cardiac and vascular functions but did not modulate survival in a murine resuscitated septic shock model |
| title_full_unstemmed | β3-Adrenergic receptor antagonism improves cardiac and vascular functions but did not modulate survival in a murine resuscitated septic shock model |
| title_short | β3-Adrenergic receptor antagonism improves cardiac and vascular functions but did not modulate survival in a murine resuscitated septic shock model |
| title_sort | β3 adrenergic receptor antagonism improves cardiac and vascular functions but did not modulate survival in a murine resuscitated septic shock model |
| topic | Septic shock Receptor Beta-3 Adrenergic Vascular reactivity |
| url | https://doi.org/10.1186/s40635-024-00705-9 |
| work_keys_str_mv | AT eugeniehagimont b3adrenergicreceptorantagonismimprovescardiacandvascularfunctionsbutdidnotmodulatesurvivalinamurineresuscitatedsepticshockmodel AT marcdamienlourencorodrigues b3adrenergicreceptorantagonismimprovescardiacandvascularfunctionsbutdidnotmodulatesurvivalinamurineresuscitatedsepticshockmodel AT benjaminglennchousterman b3adrenergicreceptorantagonismimprovescardiacandvascularfunctionsbutdidnotmodulatesurvivalinamurineresuscitatedsepticshockmodel AT francesyenpotin b3adrenergicreceptorantagonismimprovescardiacandvascularfunctionsbutdidnotmodulatesurvivalinamurineresuscitatedsepticshockmodel AT manondurand b3adrenergicreceptorantagonismimprovescardiacandvascularfunctionsbutdidnotmodulatesurvivalinamurineresuscitatedsepticshockmodel AT antoinekimmoun b3adrenergicreceptorantagonismimprovescardiacandvascularfunctionsbutdidnotmodulatesurvivalinamurineresuscitatedsepticshockmodel |