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Modulation of vascular tone by neutrophils: dependence on endothelial integrity
J L Mehta1, D L Lawson, W W Nichols
1Department of Medicine, University of Florida College of Medicine, Gainesville 32610.
Abstract:
To determine the influence of polymorphonuclear leukocytes (PMNLs) on vascular smooth muscle tone, isolated human PMNLs (10(4)-10(7) cells/ml) were suspended in a tissue bath with precontracted rat aortic rings with or without endothelium. PMNLs in low concentrations (10(4) and 10(5) cells/ml) caused a mild contraction, and in higher concentrations (10(6) and 10(7) cells/ml) caused a modest relaxation of aortic rings with intact endothelium. In contrast, PMNLs caused a potent concentration-dependent relaxation of deendothelialized rings (P less than 0.01 compared with rings with intact endothelium). The PMNL-induced vascular smooth muscle relaxation was abolished by both hemoglobin and methylene blue and potentiated by both superoxide dismutase and captopril. Although suspension of PMNLs caused release of eicosanoids, thromboxane A2 and prostacyclin, from rings with intact endothelium, neither indomethacin nor the TxA2-endoperoxide receptor antagonist SQ 29548 modified the effects of PMNLs on vascular smooth muscle tone. These observations suggest that unstimulated PMNLs generate a smooth muscle relaxant, which has biological characteristics similar to the endothelium-derived relaxing factor. Since the activity of this PMNL-derived smooth muscle relaxant is more pronounced in deendothelialized vascular segments, it appears that endothelium provides a barrier against vasorelaxation by high concentrations of PMNLs.
Insights
Polymorphonuclear leukocytes (PMNLs) can relax vascular smooth muscle, particularly when the endothelium is absent. This PMNL-derived relaxant acts similarly to endothelium-derived relaxing factor.
Area of Science:
- Vascular Biology
- Immunology
- Pharmacology
Background:
- Polymorphonuclear leukocytes (PMNLs) are key immune cells involved in inflammation.
- Vascular smooth muscle tone regulation is crucial for cardiovascular health.
- The role of PMNLs in modulating vascular tone is not fully understood.
Purpose of the Study:
- To investigate the effect of human PMNLs on vascular smooth muscle tone in rat aortic rings.
- To characterize the nature of PMNL-induced changes in vascular smooth muscle contraction and relaxation.
- To explore the potential mechanisms underlying PMNL-mediated vascular effects.
Main Methods:
- Isolated human PMNLs were incubated with precontracted rat aortic rings, both with and without intact endothelium.
- Concentration-dependent effects of PMNLs on vascular tone were assessed.
- The influence of inhibitors (hemoglobin, methylene blue) and potentiators (superoxide dismutase, captopril) was evaluated.
- Release of eicosanoids and the impact of indomethacin and SQ 29548 were examined.
Main Results:
- Low PMNL concentrations induced mild contraction, while higher concentrations caused modest relaxation in intact aortic rings.
- PMNLs induced potent, concentration-dependent relaxation in deendothelialized aortic rings.
- PMNL-induced relaxation was inhibited by hemoglobin and methylene blue, and potentiated by superoxide dismutase and captopril.
- Endothelium-derived factors like thromboxane A2 and prostacyclin were released, but did not mediate the PMNL effects.
Conclusions:
- Unstimulated PMNLs generate a smooth muscle relaxant with properties similar to endothelium-derived relaxing factor.
- The endothelium appears to act as a barrier to PMNL-induced vasorelaxation at higher PMNL concentrations.
- PMNLs may play a significant role in regulating vascular tone, especially under conditions affecting endothelial integrity.