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. 1993 Sep;110(1):151–158. doi: 10.1111/j.1476-5381.1993.tb13785.x

Involvement of nitric oxide in the endothelium-dependent relaxation induced by hydrogen peroxide in the rabbit aorta.

A Zembowicz 1, R J Hatchett 1, A M Jakubowski 1, R J Gryglewski 1
PMCID: PMC2175976  PMID: 7693274

Abstract

1. The effects of hydrogen peroxide (H2O2, 0.1-1 mM) on the tone of the rings of rabbit aorta precontracted with phenylephrine (0.2-0.3 microM) were studied. 2. H2O2 induced a concentration-dependent relaxation of both the intact and endothelium-denuded rings. However, in the presence of intact endothelium, H2O2-induced responses were 2-3 fold larger than in its absence, demonstrating the existence of endothelium-independent and endothelium-dependent components of the vasorelaxant action of H2O2. 3. The endothelium-dependent component of H2O2-induced relaxation was prevented by NG-nitro-L-arginine methyl ester (L-NAME, 30 microM) or NG-monomethyl-L-arginine (300 microM), inhibitors of nitric oxide synthase (NOS), in a manner that was reversible by L-, but not by D-arginine (2mM). The inhibitors of NOS did not affect the responses of denuded rings. 4. Methylene blue (10 microM), an inhibitor of soluble guanylate cyclase, blocked H2O2-induced relaxation of both the intact and denuded rings. 5. H2O2 (1 mM) enhanced the efflux of cyclic GMP from both the endothelium-intact and denuded rings. The effect of H2O2 was 4 fold greater in the presence of intact endothelium and this endothelium-dependent component was abolished after the inhibition of NOS by L-NAME (30 microM). 6. In contrast to the effects of H2O2, the vasorelaxant action of stable organic peroxides, tert-butyl hydroperoxide or cumene hydroperoxide, did not have an endothelium-dependent component. Moreover, they did not potentiate the efflux of cyclic GMP from the rings of rabbit aorta.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Ager A., Gordon J. L. Differential effects of hydrogen peroxide on indices of endothelial cell function. J Exp Med. 1984 Feb 1;159(2):592–603. doi: 10.1084/jem.159.2.592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Bath P. M., Hassall D. G., Gladwin A. M., Palmer R. M., Martin J. F. Nitric oxide and prostacyclin. Divergence of inhibitory effects on monocyte chemotaxis and adhesion to endothelium in vitro. Arterioscler Thromb. 1991 Mar-Apr;11(2):254–260. doi: 10.1161/01.atv.11.2.254. [DOI] [PubMed] [Google Scholar]
  4. Beckman J. S., Beckman T. W., Chen J., Marshall P. A., Freeman B. A. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1620–1624. doi: 10.1073/pnas.87.4.1620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Boucher J. L., Genet A., Vadon S., Delaforge M., Mansuy D. Formation of nitrogen oxides and citrulline upon oxidation of N omega-hydroxy-L-arginine by hemeproteins. Biochem Biophys Res Commun. 1992 May 15;184(3):1158–1164. doi: 10.1016/s0006-291x(05)80004-x. [DOI] [PubMed] [Google Scholar]
  6. Bredt D. S., Snyder S. H. Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc Natl Acad Sci U S A. 1990 Jan;87(2):682–685. doi: 10.1073/pnas.87.2.682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Burke-Wolin T. M., Wolin M. S. Inhibition of cGMP-associated pulmonary arterial relaxation to H2O2 and O2 by ethanol. Am J Physiol. 1990 May;258(5 Pt 2):H1267–H1273. doi: 10.1152/ajpheart.1990.258.5.H1267. [DOI] [PubMed] [Google Scholar]
  8. Clarke J. G., Davies G. J., Kerwin R., Hackett D., Larkin S., Dawbarn D., Lee Y., Bloom S. R., Yacoub M., Maseri A. Coronary artery infusion of neuropeptide Y in patients with angina pectoris. Lancet. 1987 May 9;1(8541):1057–1059. doi: 10.1016/s0140-6736(87)90483-1. [DOI] [PubMed] [Google Scholar]
  9. Dzau V. J., Gonzalez D., Kaempfer C., Dubin D., Wintroub B. U. Human neutrophils release serine proteases capable of activating prorenin. Circ Res. 1987 Apr;60(4):595–601. doi: 10.1161/01.res.60.4.595. [DOI] [PubMed] [Google Scholar]
  10. Feelisch M., Kelm M. Biotransformation of organic nitrates to nitric oxide by vascular smooth muscle and endothelial cells. Biochem Biophys Res Commun. 1991 Oct 15;180(1):286–293. doi: 10.1016/s0006-291x(05)81290-2. [DOI] [PubMed] [Google Scholar]
  11. Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
  12. Förstermann U., Pollock J. S., Schmidt H. H., Heller M., Murad F. Calmodulin-dependent endothelium-derived relaxing factor/nitric oxide synthase activity is present in the particulate and cytosolic fractions of bovine aortic endothelial cells. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1788–1792. doi: 10.1073/pnas.88.5.1788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gardiner S. M., Compton A. M., Bennett T., Palmer R. M., Moncada S. Control of regional blood flow by endothelium-derived nitric oxide. Hypertension. 1990 May;15(5):486–492. doi: 10.1161/01.hyp.15.5.486. [DOI] [PubMed] [Google Scholar]
  14. Goldstein I. M., Malmsten C. L., Kindahl H., Kaplan H. B., Rådmark O., Samuelsson B., Weissmann G. Thromboxane generation by human peripheral blood polymorphonuclear leukocytes. J Exp Med. 1978 Sep 1;148(3):787–792. doi: 10.1084/jem.148.3.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Hall E. D., Braughler J. M., Yonkers P. A., Smith S. L., Linseman K. L., Means E. D., Scherch H. M., Von Voigtlander P. F., Lahti R. A., Jacobsen E. J. U-78517F: a potent inhibitor of lipid peroxidation with activity in experimental brain injury and ischemia. J Pharmacol Exp Ther. 1991 Aug;258(2):688–694. [PubMed] [Google Scholar]
  17. Hamet P., Pang S. C., Tremblay J. Atrial natriuretic factor-induced egression of cyclic guanosine 3':5'-monophosphate in cultured vascular smooth muscle and endothelial cells. J Biol Chem. 1989 Jul 25;264(21):12364–12369. [PubMed] [Google Scholar]
  18. 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]
  19. Houston D. S., Shepherd J. T., Vanhoutte P. M. Adenine nucleotides, serotonin, and endothelium-dependent relaxations to platelets. Am J Physiol. 1985 Mar;248(3 Pt 2):H389–H395. doi: 10.1152/ajpheart.1985.248.3.H389. [DOI] [PubMed] [Google Scholar]
  20. Kaw S., Hecker M., Vane J. R. The two-step conversion of big endothelin 1 to endothelin 1 and degradation of endothelin 1 by subcellular fractions from human polymorphonuclear leukocytes. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6886–6890. doi: 10.1073/pnas.89.15.6886. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kimura M., Maeda K., Hayashi S. Cytosolic calcium increase in coronary endothelial cells after H2O2 exposure and the inhibitory effect of U78517F. Br J Pharmacol. 1992 Oct;107(2):488–493. doi: 10.1111/j.1476-5381.1992.tb12772.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kubes P., Suzuki M., Granger D. N. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4651–4655. doi: 10.1073/pnas.88.11.4651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kwon N. S., Nathan C. F., Gilker C., Griffith O. W., Matthews D. E., Stuehr D. J. L-citrulline production from L-arginine by macrophage nitric oxide synthase. The ureido oxygen derives from dioxygen. J Biol Chem. 1990 Aug 15;265(23):13442–13445. [PubMed] [Google Scholar]
  24. Leone A. M., Palmer R. M., Knowles R. G., Francis P. L., Ashton D. S., Moncada S. Constitutive and inducible nitric oxide synthases incorporate molecular oxygen into both nitric oxide and citrulline. J Biol Chem. 1991 Dec 15;266(35):23790–23795. [PubMed] [Google Scholar]
  25. Marletta M. A., Yoon P. S., Iyengar R., Leaf C. D., Wishnok J. S. Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry. 1988 Nov 29;27(24):8706–8711. doi: 10.1021/bi00424a003. [DOI] [PubMed] [Google Scholar]
  26. McCord J. M., Day E. D., Jr Superoxide-dependent production of hydroxyl radical catalyzed by iron-EDTA complex. FEBS Lett. 1978 Feb 1;86(1):139–142. doi: 10.1016/0014-5793(78)80116-1. [DOI] [PubMed] [Google Scholar]
  27. Mullane K. M., Salmon J. A., Kraemer R. Leukocyte-derived metabolites of arachidonic acid in ischemia-induced myocardial injury. Fed Proc. 1987 May 15;46(7):2422–2433. [PubMed] [Google Scholar]
  28. Nathan C. F., Hibbs J. B., Jr Role of nitric oxide synthesis in macrophage antimicrobial activity. Curr Opin Immunol. 1991 Feb;3(1):65–70. doi: 10.1016/0952-7915(91)90079-g. [DOI] [PubMed] [Google Scholar]
  29. Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J. 1992 Sep;6(12):3051–3064. [PubMed] [Google Scholar]
  30. O'Dea R. F., Gagnon C., Zatz M. Regulation of guanosine 3',5' cyclic monophosphate in the rat pineal and posterior pituitary glands. J Neurochem. 1978 Sep;31(3):733–738. doi: 10.1111/j.1471-4159.1978.tb07848.x. [DOI] [PubMed] [Google Scholar]
  31. Ohlstein E. H., Nichols A. J. Rabbit polymorphonuclear neutrophils elicit endothelium-dependent contraction in vascular smooth muscle. Circ Res. 1989 Oct;65(4):917–924. doi: 10.1161/01.res.65.4.917. [DOI] [PubMed] [Google Scholar]
  32. Palmer R. M., Ashton D. S., Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 1988 Jun 16;333(6174):664–666. doi: 10.1038/333664a0. [DOI] [PubMed] [Google Scholar]
  33. Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
  34. Palmer R. M., Rees D. D., Ashton D. S., Moncada S. L-arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem Biophys Res Commun. 1988 Jun 30;153(3):1251–1256. doi: 10.1016/s0006-291x(88)81362-7. [DOI] [PubMed] [Google Scholar]
  35. Radomski M. W., Palmer R. M., Moncada S. Comparative pharmacology of endothelium-derived relaxing factor, nitric oxide and prostacyclin in platelets. Br J Pharmacol. 1987 Sep;92(1):181–187. doi: 10.1111/j.1476-5381.1987.tb11310.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Rees D. D., Palmer R. M., Moncada S. Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc Natl Acad Sci U S A. 1989 May;86(9):3375–3378. doi: 10.1073/pnas.86.9.3375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Schini V., Schoeffter P., Miller R. C. Effect of endothelium on basal and on stimulated accumulation and efflux of cyclic GMP in rat isolated aorta. Br J Pharmacol. 1989 Jul;97(3):853–865. doi: 10.1111/j.1476-5381.1989.tb12025.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Schröder H., Ney P., Woditsch I., Schrör K. Cyclic GMP mediates SIN-1-induced inhibition of human polymorphonuclear leukocytes. Eur J Pharmacol. 1990 Jul 3;182(2):211–218. doi: 10.1016/0014-2999(90)90279-f. [DOI] [PubMed] [Google Scholar]
  39. Snyder S. H., Bredt D. S. Nitric oxide as a neuronal messenger. Trends Pharmacol Sci. 1991 Apr;12(4):125–128. doi: 10.1016/0165-6147(91)90526-x. [DOI] [PubMed] [Google Scholar]
  40. Stuehr D. J., Ikeda-Saito M. Spectral characterization of brain and macrophage nitric oxide synthases. Cytochrome P-450-like hemeproteins that contain a flavin semiquinone radical. J Biol Chem. 1992 Oct 15;267(29):20547–20550. [PubMed] [Google Scholar]
  41. Stuehr D. J., Kwon N. S., Nathan C. F., Griffith O. W., Feldman P. L., Wiseman J. N omega-hydroxy-L-arginine is an intermediate in the biosynthesis of nitric oxide from L-arginine. J Biol Chem. 1991 Apr 5;266(10):6259–6263. [PubMed] [Google Scholar]
  42. Tjörnhammar M. L., Lazaridis G., Bartfai T. Cyclic GMP efflux from liver slices. J Biol Chem. 1983 Jun 10;258(11):6882–6886. [PubMed] [Google Scholar]
  43. Tjörnhammar M. L., Lazaridis G., Bartfai T. Efflux of cyclic guanosine 3',5'-monophosphate from cerebellar slices stimulated by L-glutamate or high K+ or N-methyl-N'-nitro-N-nitrosoguanidine. Neurosci Lett. 1986 Jul 11;68(1):95–99. doi: 10.1016/0304-3940(86)90236-3. [DOI] [PubMed] [Google Scholar]
  44. Weiss S. J., Young J., LoBuglio A. F., Slivka A., Nimeh N. F. Role of hydrogen peroxide in neutrophil-mediated destruction of cultured endothelial cells. J Clin Invest. 1981 Sep;68(3):714–721. doi: 10.1172/JCI110307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. White K. A., Marletta M. A. Nitric oxide synthase is a cytochrome P-450 type hemoprotein. Biochemistry. 1992 Jul 28;31(29):6627–6631. doi: 10.1021/bi00144a001. [DOI] [PubMed] [Google Scholar]
  46. Wintroub B. U., Klickstein L. B., Dzau V. J., Watt K. W. Granulocyte-angiotensin system. Identification of angiotensinogen as the plasma protein substrate of leukocyte cathepsin G. Biochemistry. 1984 Jan 17;23(2):227–232. doi: 10.1021/bi00297a009. [DOI] [PubMed] [Google Scholar]
  47. Wolin M. S., Burke T. M. Hydrogen peroxide elicits activation of bovine pulmonary arterial soluble guanylate cyclase by a mechanism associated with its metabolism by catalase. Biochem Biophys Res Commun. 1987 Feb 27;143(1):20–25. doi: 10.1016/0006-291x(87)90623-1. [DOI] [PubMed] [Google Scholar]
  48. Woods M., Houslay M. D. Desensitization of atriopeptin stimulated accumulation and extrusion of cyclic GMP from a kidney epithelial cell line (MDCK). Biochem Pharmacol. 1991 Feb 1;41(3):385–394. doi: 10.1016/0006-2952(91)90535-d. [DOI] [PubMed] [Google Scholar]
  49. Zembowicz A., Hecker M., Macarthur H., Sessa W. C., Vane J. R. Nitric oxide and another potent vasodilator are formed from NG-hydroxy-L-arginine by cultured endothelial cells. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11172–11176. doi: 10.1073/pnas.88.24.11172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Zembowicz A., Swierkosz T. A., Southan G. J., Hecker M., Gryglewski R. J., Vane J. R. Mechanisms of the endothelium-dependent relaxation induced by NG-hydroxy-L-arginine. J Cardiovasc Pharmacol. 1992;20 (Suppl 12):S57–S59. doi: 10.1097/00005344-199204002-00017. [DOI] [PubMed] [Google Scholar]

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