Related Experiment Video
Updated: Apr 11, 2026
Standardized Colon Ascendens Stent Peritonitis in Rats - a Simple, Feasible Animal Model to Induce Septic Acute Kidney Injury
Published on: February 15, 2022
Gadolinium chloride modulates bradykinin-induced pulmonary vasoconstriction and hypoxic pulmonary vasoconstriction
Stefan Lauer1, Lars G Fischer, Hugo K Van Aken
11Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital of Muenster , Muenster , Germany.
Background:
Macrophages importantly contribute to sepsis-induced lung injury. As their impact on pulmonary endothelial injury and dysregulation of hypoxic pulmonary vasoconstriction (HPV) remains unclear, we assessed pulmonary endothelial dysfunction and HPV by macrophage inhibition via gadolinium chloride (GC) pre-treatment in rats with peritonitis (cecal ligation and puncture [CLP]).
Methods:
The following four study groups were made: Group I: SHAM and group II: SHAM + GC (pre-treatment with NaCl 0.9% or GC 14 mg/kg body weight (b.w.) intravenously 24 hours prior to sham laparotomy); group III: CLP and group IV: CLP + GC (pre-treatment with NaCl 0.9% or GC 14 mg/kg b.w. 24 hours prior to induction of peritonitis). Exhaled nitric oxide (exNO), bradykinin-induced pulmonary vasoconstriction (=surrogate marker of endothelial dysfunction) and HPV were investigated in isolated and perfused lungs (n = 40). Using the same protocol wet to dry lung weight ratio and myeloperoxidase (MPO) activity were investigated in separate rats (n = 28). In additional rats (n = 12) of groups III and IV nitrite levels in alveolar macrophages (AM) were measured.
Results:
In sepsis, GC pre-treatment significantly attenuated exNO levels, AM-derived nitrite levels, lung MPO activity, and restored blunted HPV, but severely enhanced endothelial dysfunction in healthy and septic animals.
Conclusion:
Macrophages exhibit a controversial role in sepsis-induced lung injury. The GC-induced restoration of inflammation parameters to sham levels is clearly limited by the negative impact on CLP-induced endothelial injury in this setting. The exact link between the GC-associated modulation of the NO pathway demonstrated and septic lung injury needs to be determined in future studies.
Insights
Gadolinium chloride (GC) pre-treatment in sepsis models reduced inflammation and improved hypoxic pulmonary vasoconstriction (HPV). However, it worsened endothelial dysfunction, indicating macrophages have a complex role in lung injury.
Area of Science:
- Pulmonary Medicine
- Sepsis Research
- Inflammation Biology
Background:
- Macrophages play a key role in sepsis-induced lung injury.
- The specific impact of macrophages on pulmonary endothelial injury and hypoxic pulmonary vasoconstriction (HPV) during sepsis is not well understood.
Purpose of the Study:
- To investigate the role of macrophages in sepsis-induced lung injury, specifically their effect on pulmonary endothelial dysfunction and HPV.
- To assess the impact of macrophage inhibition using gadolinium chloride (GC) on these processes in a rat model of sepsis.
Main Methods:
- Rats underwent either sham laparotomy or cecal ligation and puncture (CLP) to induce sepsis.
- Animals were pre-treated with either saline or gadolinium chloride (GC).
- Pulmonary endothelial function (bradykinin-induced vasoconstriction), HPV, exhaled nitric oxide (exNO), lung MPO activity, and nitrite levels in alveolar macrophages (AM) were measured.
Main Results:
- GC pre-treatment attenuated exhaled nitric oxide (exNO) levels, AM-derived nitrite, and lung MPO activity in septic rats.
- GC pre-treatment restored blunted hypoxic pulmonary vasoconstriction (HPV) in septic rats.
- Conversely, GC pre-treatment severely enhanced endothelial dysfunction in both healthy and septic animals.
Conclusions:
- Macrophages play a complex and controversial role in sepsis-induced lung injury.
- While GC-induced reduction in inflammation and restoration of HPV were observed, this was counteracted by significant endothelial injury.
- Further research is needed to elucidate the precise link between GC-modulated nitric oxide pathways and septic lung injury.
