Interaction of neutrophils with vascular smooth muscle: identification of a neutrophil-derived relaxing factor.
Experiments were designed to study the interaction of rat peritoneal neutrophils with the vascular smooth muscle of the rat aorta. Rings of aorta, suspended in 10-ml organ chambers containing a physiologic salt solution, were precontracted with phenylephrine. Neutrophils (1 X 10(5) -4 X 10(7) cells/organ chamber) caused a cell number-dependent relaxation of the rat aorta that was augmented by superoxide dismutase (100 U/ml) or changing the oxygen content from 95 to 21%. The neutrophil-induced smooth muscle relaxation occurred in rings with and without endothelium and in rings precontracted with increasing concentrations of phenylephrine, prostaglandin F2 alpha or KCI. Catalase (1000 U/ml) and mannitol (1 X 10(-3) M) did not block the neutrophil-induced relaxation, whereas phenazine methosulfate (1 X 10(-5) M), hydroquinone (3 X 10(-5) M) and methylene blue (1 X 10(-5) M) reversed the neutrophil-induced relaxation. Pre-exposure of endothelium-rubbed rings to neutrophils (2 X 10(7) cells/organ chamber; 15 min) depressed the subsequent concentration-response curve to phenylephrine but augmented the relaxation induced by the phosphodiesterase inhibitor zaprinast (1 X 10(-5) M). The effluent from a column restraining the neutrophils induced a relaxation of endothelium-rubbed aortic rings that was prevented by methylene blue (1 X 10(-5) M). These results demonstrate that rat neutrophils release a factor that has a pharmacologic profile similar to that previously reported for the relaxing factor released from the vascular endothelium.
D000818:Animals; D001688:Biological Products / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D046508:Culture Techniques; D015237:Dinoprost; D004730:Endothelium, Vascular / Q000187:drug effects; D006873:Hydroquinones / Q000494:pharmacology; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D008751:Methylene Blue / Q000494:pharmacology; D008773:Methylphenazonium Methosulfate / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009504:Neutrophils / Q000378:metabolism*; D009569:Nitric Oxide; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D013482:Superoxide Dismutase / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D001688:Biological Products; D006873:Hydroquinones; D011460:Prostaglandins F; D014665:Vasodilator Agents; D010656:Phenylephrine; D008773:Methylphenazonium Methosulfate; D009569:Nitric Oxide; D008353:Mannitol; D011189:Potassium Chloride; D015237:Dinoprost; D002374:Catalase; D013482:Superoxide Dismutase; D008751:Methylene Blue; C031927:hydroquinone