Abstract
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.
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Selected References
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- Auch-Schwelk W., Katusic Z. S., Vanhoutte P. M. Contractions to oxygen-derived free radicals are augmented in aorta of the spontaneously hypertensive rat. Hypertension. 1989 Jun;13(6 Pt 2):859–864. doi: 10.1161/01.hyp.13.6.859. [DOI] [PubMed] [Google Scholar]
- Babior B. M., Kipnes R. S., Curnutte J. T. Biological defense mechanisms. The production by leukocytes of superoxide, a potential bactericidal agent. J Clin Invest. 1973 Mar;52(3):741–744. doi: 10.1172/JCI107236. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burke T. M., Wolin M. S. Hydrogen peroxide elicits pulmonary arterial relaxation and guanylate cyclase activation. Am J Physiol. 1987 Apr;252(4 Pt 2):H721–H732. doi: 10.1152/ajpheart.1987.252.4.H721. [DOI] [PubMed] [Google Scholar]
- Carden D. L., Smith J. K., Korthuis R. J. Neutrophil-mediated microvascular dysfunction in postischemic canine skeletal muscle. Role of granulocyte adherence. Circ Res. 1990 May;66(5):1436–1444. doi: 10.1161/01.res.66.5.1436. [DOI] [PubMed] [Google Scholar]
- Carpenter L. J., Johnson K. J., Kunkel R. G., Roth R. A. Phorbol myristate acetate produces injury to isolated rat lungs in the presence and absence of perfused neutrophils. Toxicol Appl Pharmacol. 1987 Oct;91(1):22–32. doi: 10.1016/0041-008x(87)90190-6. [DOI] [PubMed] [Google Scholar]
- Chobanian A. V., Prescott M. F., Haudenschild C. C. Recent advances in molecular pathology. The effects of hypertension on the arterial wall. Exp Mol Pathol. 1984 Aug;41(1):153–169. doi: 10.1016/0014-4800(84)90015-7. [DOI] [PubMed] [Google Scholar]
- De Kimpe S. J., Van Heuven-Nolsen D., Nijkamp F. P. Bovine polymorphonuclear leukocytes increase sensitivity to noradrenaline in isolated mesenteric arteries. Br J Pharmacol. 1992 Mar;105(3):581–586. doi: 10.1111/j.1476-5381.1992.tb09022.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Feigen L. P. Differential effects of leukotrienes C4, D4 and E4 in the canine renal and mesenteric vascular beds. J Pharmacol Exp Ther. 1983 Jun;225(3):682–687. [PubMed] [Google Scholar]
- Gillespie M. N., Kojima S., Kunitomo M., Jay M. Coronary and myocardial effects of activated neutrophils in perfused rabbit hearts. J Pharmacol Exp Ther. 1986 Dec;239(3):836–840. [PubMed] [Google Scholar]
- Gryglewski R. J., Palmer R. M., Moncada S. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature. 1986 Apr 3;320(6061):454–456. doi: 10.1038/320454a0. [DOI] [PubMed] [Google Scholar]
- Gyllenhammar H. Lucigenin chemiluminescence in the assessment of neutrophil superoxide production. J Immunol Methods. 1987 Mar 12;97(2):209–213. doi: 10.1016/0022-1759(87)90461-3. [DOI] [PubMed] [Google Scholar]
- Harlan J. M., Callahan K. S. Role of hydrogen peroxide in the neutrophil-mediated release of prostacyclin from cultured endothelial cells. J Clin Invest. 1984 Aug;74(2):442–448. doi: 10.1172/JCI111440. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Henricks P. A., Binkhorst G. J., Nijkamp F. P. Stress diminishes infiltration and oxygen metabolism of phagocytic cells in calves. Inflammation. 1987 Dec;11(4):427–437. doi: 10.1007/BF00915986. [DOI] [PubMed] [Google Scholar]
- Koga T., Takata Y., Kobayashi K., Takishita S., Yamashita Y., Fujishima M. Age and hypertension promote endothelium-dependent contractions to acetylcholine in the aorta of the rat. Hypertension. 1989 Nov;14(5):542–548. doi: 10.1161/01.hyp.14.5.542. [DOI] [PubMed] [Google Scholar]
- Lawson D. L., Mehta J. L., Nichols W. W., Mehta P., Donnelly W. H. Superoxide radical-mediated endothelial injury and vasoconstriction of rat thoracic aortic rings. J Lab Clin Med. 1990 May;115(5):541–548. [PubMed] [Google Scholar]
- Lee D. K., Faunce D., Henry D., Sturm R. J., Rimele T. Neutrophil-derived relaxing factor relaxes vascular smooth muscle through a cGMP-mediated mechanism. Life Sci. 1990;46(21):1531–1538. doi: 10.1016/0024-3205(90)90426-r. [DOI] [PubMed] [Google Scholar]
- Lüscher T. F. The endothelium. Target and promoter of hypertension? Hypertension. 1990 May;15(5):482–485. doi: 10.1161/01.hyp.15.5.482. [DOI] [PubMed] [Google Scholar]
- Mehta J. L., Lawson D. L., Nichols W. W., Mehta P. Modulation of vascular tone by neutrophils: dependence on endothelial integrity. Am J Physiol. 1989 Oct;257(4 Pt 2):H1315–H1320. doi: 10.1152/ajpheart.1989.257.4.H1315. [DOI] [PubMed] [Google Scholar]
- Nishida M., Kuzuya T., Hoshida S., Kim Y., Kitabatake A., Kamada T., Tada M. Polymorphonuclear leukocytes induced vasoconstriction in isolated canine coronary arteries. Circ Res. 1990 Jan;66(1):253–258. doi: 10.1161/01.res.66.1.253. [DOI] [PubMed] [Google Scholar]
- Pieper G. M., Gross G. J. Selective impairment of endothelium-dependent relaxation by oxygen-derived free radicals: distinction between receptor versus nonreceptor mediators. Blood Vessels. 1989;26(1):44–47. [PubMed] [Google Scholar]
- Schmid-Schönbein G. W., Engler R. L. Granulocytes as active participants in acute myocardial ischemia and infarction. Am J Cardiovasc Pathol. 1987 Jan;1(1):15–30. [PubMed] [Google Scholar]
- Sessa W. C., Mullane K. M. Release of a neutrophil-derived vasoconstrictor agent which augments platelet-induced contractions of blood vessels in vitro. Br J Pharmacol. 1990 Mar;99(3):553–559. doi: 10.1111/j.1476-5381.1990.tb12967.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shimokawa H., Vanhoutte P. M. Impaired endothelium-dependent relaxation to aggregating platelets and related vasoactive substances in porcine coronary arteries in hypercholesterolemia and atherosclerosis. Circ Res. 1989 May;64(5):900–914. doi: 10.1161/01.res.64.5.900. [DOI] [PubMed] [Google Scholar]
- Sirén A. L., Feuerstein G. Effects of PAF and BN 52021 on cardiac function and regional blood flow in conscious rats. Am J Physiol. 1989 Jul;257(1 Pt 2):H25–H32. doi: 10.1152/ajpheart.1989.257.1.H25. [DOI] [PubMed] [Google Scholar]
- Taylor L., Menconi M. J., Polgar P. The participation of hydroperoxides and oxygen radicals in the control of prostaglandin synthesis. J Biol Chem. 1983 Jun 10;258(11):6855–6857. [PubMed] [Google Scholar]
- Todoki K., Okabe E., Kiyose T., Sekishita T., Ito H. Oxygen free radical-mediated selective endothelial dysfunction in isolated coronary artery. Am J Physiol. 1992 Mar;262(3 Pt 2):H806–H812. doi: 10.1152/ajpheart.1992.262.3.H806. [DOI] [PubMed] [Google Scholar]
- Tsao P. S., Ma X. L., Lefer A. M. Activated neutrophils aggravate endothelial dysfunction after reperfusion of the ischemic feline myocardium. Am Heart J. 1992 Jun;123(6):1464–1471. doi: 10.1016/0002-8703(92)90796-x. [DOI] [PubMed] [Google Scholar]
- Vane J. R., Anggård E. E., Botting R. M. Regulatory functions of the vascular endothelium. N Engl J Med. 1990 Jul 5;323(1):27–36. doi: 10.1056/NEJM199007053230106. [DOI] [PubMed] [Google Scholar]
- Vanhoutte P. M. Endothelium and control of vascular function. State of the Art lecture. Hypertension. 1989 Jun;13(6 Pt 2):658–667. doi: 10.1161/01.hyp.13.6.658. [DOI] [PubMed] [Google Scholar]
- Wang J. H., Chen H. S., Wang T., Diao Y. F., Tian K. L. Oxygen-derived free radicals induced cellular injury in superior mesenteric artery occlusion shock: protective effect of superoxide dismutase. Circ Shock. 1990 Sep;32(1):31–41. [PubMed] [Google Scholar]
- Ward P. A., Varani J. Mechanisms of neutrophil-mediated killing of endothelial cells. J Leukoc Biol. 1990 Jul;48(1):97–102. doi: 10.1002/jlb.48.1.97. [DOI] [PubMed] [Google Scholar]
- Wei E. P., Kontos H. A., Christman C. W., DeWitt D. S., Povlishock J. T. Superoxide generation and reversal of acetylcholine-induced cerebral arteriolar dilation after acute hypertension. Circ Res. 1985 Nov;57(5):781–787. doi: 10.1161/01.res.57.5.781. [DOI] [PubMed] [Google Scholar]
- Werns S. W., Lucchesi B. R. Free radicals and ischemic tissue injury. Trends Pharmacol Sci. 1990 Apr;11(4):161–166. doi: 10.1016/0165-6147(90)90068-J. [DOI] [PubMed] [Google Scholar]
- Whorton A. R., Montgomery M. E., Kent R. S. Effect of hydrogen peroxide on prostaglandin production and cellular integrity in cultured porcine aortic endothelial cells. J Clin Invest. 1985 Jul;76(1):295–302. doi: 10.1172/JCI111960. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wolin M. S. Activated oxygen metabolites as regulators of vascular tone. Klin Wochenschr. 1991 Dec 15;69(21-23):1046–1049. doi: 10.1007/BF01645156. [DOI] [PubMed] [Google Scholar]
