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Inhibition by a stable factor derived from neutrophils of endothelium-dependent relaxation in rat aorta
1Department of Cardiac Surgery, University of Melbourne Austin Hospital, Heidelberg, Victoria, Australia.
Abstract:
Polymorphonuclear leukocytes (PMNs) may play an important role in many pathophysiological states. The effect of a factor derived from PMNs on endothelium-dependent relaxation was studied using rat aortic rings in organ chambers. PMNs were obtained from cardiac surgical patients and healthy volunteers. After incubation in Krebs solution for 3 h, supernatants of PMN suspensions were isolated and used to pretreat the aortic rings for 30 min. The results showed that the supernatants derived from 1 x 10(4) to 5 x 10(6) cells/ml PMNs produced a concentration-dependent inhibition of endothelium-dependent relaxation to acetylcholine but not endothelium-independent relaxation to sodium nitroprusside. The effect could not be prevented by oxygen free radical scavenger superoxide dismutase (150 U/ml), catalase (1,200 U/ml), or mannitol (20 mM) used alone or in combination. Heating the supernatants at 95 degrees C for 30 min did not reduce the inhibitory effect. L-Arginine at 3 x 10(-5) to 3 x 10(-3) M did not significantly reverse the inhibitory effect of the PMN-derived factor. In conclusion, this study reveals that a heat-stable factor derived from human PMNs potently inhibits acetylcholine-induced endothelium-dependent relaxation but not sodium nitroprusside-induced endothelium-independent relaxation in rat aorta. This inhibitory effect is not caused by oxygen free radicals, a limitation of nitric oxide precursor or other unstable factors.
Insights
A heat-stable factor from polymorphonuclear leukocytes (PMNs) inhibits blood vessel relaxation. This discovery offers new insights into cardiovascular health and disease mechanisms.
Area of Science:
- Cardiovascular Biology
- Immunology
- Vascular Physiology
Background:
- Polymorphonuclear leukocytes (PMNs) are implicated in various disease states.
- Understanding PMN-derived factors is crucial for cardiovascular research.
Purpose of the Study:
- To investigate the effect of a PMN-derived factor on endothelium-dependent and independent vasodilation.
- To characterize the nature of this inhibitory factor.
Main Methods:
- Rat aortic rings were pretreated with PMN supernatants.
- Endothelium-dependent relaxation to acetylcholine and endothelium-independent relaxation to sodium nitroprusside were measured.
- The effects of scavengers, heat, and L-arginine were assessed.
Main Results:
- PMN supernatants caused a concentration-dependent inhibition of acetylcholine-induced relaxation.
- This inhibition was observed for endothelium-dependent relaxation but not endothelium-independent relaxation.
- The inhibitory factor was heat-stable and not neutralized by oxygen radical scavengers or L-arginine.
Conclusions:
- A heat-stable, non-radical, PMN-derived factor potently inhibits endothelium-dependent vasodilation.
- This factor does not appear to involve nitric oxide precursor limitation.
- Further research is needed to identify the specific factor and its role in pathophysiology.