Leukocyte-induced endothelial dysfunction in the rabbit basilar artery: modulation by platelet-activating factor

Area of Science:

• Vascular biology
• Immunology
• Endothelial function

Background:

• Polymorphonuclear leukocytes (PMNLs) play a role in vascular inflammation.
• Endothelial dysfunction is a key factor in cardiovascular diseases.
• N-formyl-methionyl-leucyl-phenylalanine (fMLP) is a potent activator of PMNLs.

Purpose of the Study:

• To investigate the impact of activated PMNLs on endothelium-dependent relaxation of the rabbit basilar artery (BA).
• To determine the role of platelet-activating factor (PAF) in modulating PMNL-induced endothelial dysfunction.

Main Methods:

• Isolated rabbit basilar artery (BA) segments were used in organ bath studies.
• Endothelium-dependent relaxation was assessed using acetylcholine (ACh) and bradykinin.
• Endothelium-independent relaxation was measured with nitroprusside.
• PMNL activation was induced by fMLP, with or without PAF.
• Beta-glucuronidase activity was measured to assess PMNL exocytosis.
• Scanning electron microscopy (SEM) was used to examine endothelial morphology.

Main Results:

• Activated PMNLs significantly reduced endothelium-dependent relaxation to ACh and bradykinin (p < 0.05).
• PMNLs did not affect endothelium-independent relaxation to nitroprusside.
• Low concentrations of PAF potentiated PMNL-induced inhibition of relaxation.
• PAF enhanced PMNL exocytosis and caused more apparent endothelial microlesions.
• PAF enabled PMNLs to induce dysfunction at lower cell concentrations and shorter contact times.

Conclusions:

• Activated PMNLs significantly impair endothelium-dependent vasodilation.
• Platelet-activating factor (PAF) acts as a potentiator, increasing PMNL aggression towards the endothelium.
• PAF-mediated potentiation of PMNLs leads to exacerbated endothelial dysfunction and morphological damage.