Pathophysiological role of endothelins in pulmonary microcirculatory disorders due to intestinal ischemia and reperfusion
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Published on: September 27, 2024
H Mitsuoka1, N Unno, T Sakurai
1Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Background:
This study was conducted to investigate pulmonary microcirculatory disorders caused by intestinal ischemia reperfusion (IIR), and the pathophysiological roles of endothelin (ET) in acute lung injury (ALI).
Methods:
Male rats were pretreated with normal saline or a nonselective ET receptor antagonist (TAK-044) and subjected to IIR (60 min of intestinal ischemia and 180 min of reperfusion). The right upper lobe of the lung was examined by intravital confocal microscopy.
Results:
The size of arterioles and venules was not significantly reduced during IIR, but the functional capillary density (FCD) decreased significantly. TAK-044 improved the pulmonary microhemodynamics, inhibiting the accumulation of leukocytes, the pulmonary edema, and the decrease of FCD.
Conclusions:
In the early stage of IIR, pulmonary microhemodynamics seemed more likely to be disturbed by the decrease of FCD, than by arteriolar or venular vasoconstriction. ETs decrease the FCD, promoting the interaction between leukocytes and pulmonary vessels.
Insights
Intestinal ischemia reperfusion (IIR) impairs lung microcirculation by reducing functional capillary density (FCD). Endothelin (ET) antagonists improve lung hemodynamics and reduce injury during IIR.
Area of Science:
- Physiology
- Pathology
- Pharmacology
Background:
- Intestinal ischemia reperfusion (IIR) can lead to acute lung injury (ALI).
- The role of endothelin (ET) in IIR-induced pulmonary microcirculatory disorders is not fully understood.
Purpose of the Study:
- To investigate pulmonary microcirculatory disorders during IIR.
- To elucidate the pathophysiological role of endothelin (ET) in acute lung injury (ALI) following IIR.
Main Methods:
- Male rats were subjected to IIR (60 min ischemia, 180 min reperfusion).
- Rats were pretreated with saline or a nonselective ET receptor antagonist (TAK-044).
- Pulmonary microcirculation was examined using intravital confocal microscopy.
Main Results:
- IIR significantly decreased functional capillary density (FCD) but did not alter arteriolar or venular size.
- TAK-044 treatment improved pulmonary microhemodynamics.
- TAK-044 inhibited leukocyte accumulation, pulmonary edema, and the decrease in FCD.
Conclusions:
- Pulmonary microhemodynamic disturbances in early IIR are primarily due to decreased FCD, not vasoconstriction.
- Endothelin (ET) contributes to IIR-induced ALI by reducing FCD and promoting leukocyte-endothelial interactions.
