Bovine polymorphonuclear leukocytes increase sensitivity to noradrenaline in isolated mesenteric arteries.
1. The effects of polymorphonuclear leukocytes (PMN) on vascular function to (-)-noradrenaline were examined in vitro. Purified bovine PMN were incubated in siliconized organ baths containing rings of bovine mesenteric arteries, after which a concentration-effect curve in response to (-)-noradrenaline was obtained. 2. PMN-derived products induced a long lasting concentration-dependent contraction of the blood vessels generating 24.4 +/- 6.8% of the maximal tension to (-)-noradrenaline at a cell concentration of 2.5 x 10(6) ml-1. The contractile response was also found in endothelium-denuded vascular rings. 3. PMN present in the organ bath caused an increase in the sensitivity of vascular rings to (-)-noradrenaline. At a cell number of 2.5 x 10(6) PMN ml-1 the pD2-value for (-)-noradrenaline was augmented 0.40 +/- 0.05 (P less than 0.001), while total contraction at the highest concentration (-)-noradrenaline was not affected. This increase in sensitivity was dependent on an intact endothelium. 4. The increase in sensitivity to (-)-noradrenaline by PMN was inhibited by superoxide dismutase, but not by catalase, dimethylthiourea, indomethacin or nordihydroguaiaretic acid. The non-stimulated bovine PMN produced oxygen radicals as measured by chemiluminescence. 5. Simultaneous incubation of PMN and (-)-noradrenaline with arterial rings induced an increase in the release of prostacyclin, measured by an elevated concentration of 6-keto-prostaglandin F1 alpha in the supernatant. 6. It is concluded that PMN can increase vascular tone directly or indirectly probably via the interaction of PMN-derived superoxide anions with endothelium-derived relaxing factor.
De Kimpe
S J
SJ
Dept. of Pharmacology, Faculty of Pharmacy, University of Utrecht, The Netherlands.
Van Heuven-Nolsen
D
D
Nijkamp
F P
FP
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002417:Cattle; D016166:Free Radical Scavengers; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009504:Neutrophils / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology*; D011863:Radioimmunoassay; D013929:Thromboxane B2 / Q000096:biosynthesis; D019323:omega-N-Methylarginine
D016166:Free Radical Scavengers; D019323:omega-N-Methylarginine; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D001120:Arginine; D009638:Norepinephrine