Rabbit polymorphonuclear neutrophils elicit endothelium-dependent contraction in vascular smooth muscle.
The present studies were designed to investigate the interaction between activated polymorphonuclear neutrophils (PMNs) and endothelial regulation of vascular smooth muscle function. Rabbit peritoneal PMNs (4 x 10(3)-4 x 10(5) cells/ml) added to muscle bath chambers containing phenylephrine-precontracted rabbit isolated aortic rings produced no effect on vascular tone. However, when PMNs were activated with the chemotactic peptide, f-met-leu-phe (0.1 microM), PMNs produced concentration-dependent vascular contraction, which was dependent on the presence of the endothelium. Aortic rings denuded of endothelium were unaffected by activated PMNs. Superoxide dismutase (100 units/ml) treatment of tissues blocked completely PMN-induced vascular contraction, whereas mannitol (20 mM) had no significant effect on PMN-induced vascular contraction. Pyrogallol (a generator of superoxide anion) produced a response that was similar to that observed with activated PMNs. Superoxide anion production was measured separately, and the time of peak rate of superoxide anion production corresponded to the time of the maximal vascular contractile responses. Activated PMNs added to vascular tissues undergoing endothelium-dependent relaxation mediated by either acetylcholine or A23187 produced a reversal of vascular relaxation. Furthermore, activated PMNs did not have any effect on endothelium-independent vascular relaxation produced by either isoproterenol or nitroglycerin. The present investigation reveals that activated PMNs can release superoxide anion and produce endothelium-dependent contraction. The endothelium-dependent contraction may be the result of superoxide anion inactivation of endothelium-derived relaxing factor.
Ohlstein
E H
EH
Department of Pharmacology, Smith Kline & French Laboratories, King of Prussia, Pennsylvania.
Nichols
A J
AJ
D000818:Animals; D000838:Anions / Q000378:metabolism; D001011:Aorta / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D005609:Free Radicals; D006878:Hydroxides / Q000494:pharmacology; D017665:Hydroxyl Radical; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology; D011817:Rabbits; D013481:Superoxides / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects
D000838:Anions; D005609:Free Radicals; D006878:Hydroxides; D013481:Superoxides; D009569:Nitric Oxide; D017665:Hydroxyl Radical