Acetylcholine-induced relaxation in bovine isolated mesenteric arteries is suppressed by polymorphonuclear leukocytes.
1. The endothelium plays a critical role in maintaining vascular tone via generation of potent vasoconstrictor and dilator substances. We examined the effect of bovine purified polymorphonuclear leukocytes (PMN) on the endothelium-dependent relaxation to acetylcholine in isolated mesenteric arteries. 2. In the presence of PMN (2.5 x 10(6) cells ml-1) the maximal relaxation to acetylcholine was decreased from 76.1 +/- 2.4% to 44.9 +/- 7.4% of the precontraction (P < 0.001). This effect was inhibited by superoxide dismutase and NG-mono-methyl-L-arginine, but not by catalase or indomethacin. 3. PMN were not able to influence significantly the endothelium-independent relaxation to nitroprusside. 4. Removal of PMN after preincubation and prior to precontraction and relaxation did not influence the acetylcholine-induced relaxation, indicating that no irreversible vascular damage had occurred. 5. Superoxide anion production by unstimulated PMN was less than 10% compared to phorbol myristate acetate-activated PMN, measured by chemiluminescence and reduction of ferricytochrome c. 6. We conclude that small amounts of superoxide anions produced by unstimulated PMN contribute to a decrease in relaxation to acetylcholine by interfering with endothelium-derived nitric oxide.
De Kimpe
S J
SJ
Department of Pharmacology, Faculty of Pharmacy, Utrecht University, The Netherlands.
Van Heuven-Nolsen
D
D
Nijkamp
F P
FP
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D002417:Cattle; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D016166:Free Radical Scavengers; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D019323:omega-N-Methylarginine
D016166:Free Radical Scavengers; D013481:Superoxides; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D001120:Arginine; D002374:Catalase; D013482:Superoxide Dismutase; D000109:Acetylcholine; D007213:Indomethacin