Inhibition by a stable factor derived from neutrophils of endothelium-dependent relaxation in rat aorta.
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.
Liu
J J
JJ
Department of Cardiac Surgery, University of Melbourne Austin Hospital, Heidelberg, Victoria, Australia.
Chen
J R
JR
Wiley
J
J
Johnston
C C
CC
Buxton
B F
BF
D000818:Animals; D001011:Aorta / Q000187:drug effects*; D001120:Arginine / Q000494:pharmacology; D004355:Drug Stability; D004730:Endothelium, Vascular / Q000187:drug effects*; D006358:Hot Temperature; D006801:Humans; D066298:In Vitro Techniques; D009504:Neutrophils / Q000378:metabolism*; D051381:Rats; D014664:Vasodilation / Q000187:drug effects*
D001120:Arginine