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. 1995 Sep;116(2):1906–1910. doi: 10.1111/j.1476-5381.1995.tb16681.x

Discrimination by the NO-trapping agent, carboxy-PTIO, between NO and the nitrergic transmitter but not between NO and EDRF.

M J Rand 1, C G Li 1
PMCID: PMC1909095  PMID: 8528578

Abstract

1. The effects of carboxy-PTIO, a scavenger of free radical nitric oxide (NO), were studied on endothelium-dependent relaxations of rat aorta and nitrergic nerve stimulation-induced relaxations of anococcygeus muscle and gastric fundus strips to test the hypothesis that endothelium-derived relaxing factor (EDRF) and the transmitter released by nitrergic nerves is free radical NO. 2. Carboxy-PTIO (10-300 microM) produced concentration-dependent reductions of relaxations elicited by exogenous NO, and relaxations mediated by EDRF released by acetylcholine and ATP in rings of rat aorta. The inhibitory effect of carboxy-PTIO was removed by washing the tissues. 3. In the rat anococcygeus muscle, carboxy-PTIO (10-300 microM) produced concentration-dependent reductions of relaxations to exogenous NO; however, in concentrations up to 2000 microM it did not reduce relaxations elicited by nitrergic nerve stimulation (1-2 Hz), in fact, concentrations of 300 microM or more slightly enhanced them. 4. In rat gastric fundus strips, carboxy-PTIO (100 and 300 microM) reduced relaxations to exogenous NO, but relaxations elicited by stimulation of the nitrergic component of non-adrenergic, non-cholinergic nerves were not affected. 5. These results suggest that EDRF is free radical NO and may be designated EDNO, but the transmitter released from nitrergic nerves does not appear to be identical to EDNO and may not be free radical NO.

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Selected References

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  1. Akaike T., Yoshida M., Miyamoto Y., Sato K., Kohno M., Sasamoto K., Miyazaki K., Ueda S., Maeda H. Antagonistic action of imidazolineoxyl N-oxides against endothelium-derived relaxing factor/.NO through a radical reaction. Biochemistry. 1993 Jan 26;32(3):827–832. doi: 10.1021/bi00054a013. [DOI] [PubMed] [Google Scholar]
  2. Assreuy J., Cunha F. Q., Liew F. Y., Moncada S. Feedback inhibition of nitric oxide synthase activity by nitric oxide. Br J Pharmacol. 1993 Mar;108(3):833–837. doi: 10.1111/j.1476-5381.1993.tb12886.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barbier A. J., Lefebvre R. A. Effect of LY 83583 on relaxation induced by non-adrenergic non-cholinergic nerve stimulation and exogenous nitric oxide in the rat gastric fundus. Eur J Pharmacol. 1992 Aug 25;219(2):331–334. doi: 10.1016/0014-2999(92)90315-u. [DOI] [PubMed] [Google Scholar]
  4. Bates J. N., Harrison D. G., Myers P. R., Minor R. L. EDRF: nitrosylated compound or authentic nitric oxide. Basic Res Cardiol. 1991;86 (Suppl 2):17–26. doi: 10.1007/978-3-642-72461-9_3. [DOI] [PubMed] [Google Scholar]
  5. Boeckxstaens G. E., De Man J. G., De Winter B. Y., Herman A. G., Pelckmans P. A. Pharmacological similarity between nitric oxide and the nitrergic neurotransmitter in the canine ileocolonic junction. Eur J Pharmacol. 1994 Oct 13;264(1):85–89. doi: 10.1016/0014-2999(94)90640-8. [DOI] [PubMed] [Google Scholar]
  6. Dinerman J. L., Steiner J. P., Dawson T. M., Dawson V., Snyder S. H. Cyclic nucleotide dependent phosphorylation of neuronal nitric oxide synthase inhibits catalytic activity. Neuropharmacology. 1994 Nov;33(11):1245–1251. doi: 10.1016/0028-3908(94)90023-x. [DOI] [PubMed] [Google Scholar]
  7. Feelisch M., te Poel M., Zamora R., Deussen A., Moncada S. Understanding the controversy over the identity of EDRF. Nature. 1994 Mar 3;368(6466):62–65. doi: 10.1038/368062a0. [DOI] [PubMed] [Google Scholar]
  8. Gibson A., Babbedge R., Brave S. R., Hart S. L., Hobbs A. J., Tucker J. F., Wallace P., Moore P. K. An investigation of some S-nitrosothiols, and of hydroxy-arginine, on the mouse anococcygeus. Br J Pharmacol. 1992 Nov;107(3):715–721. doi: 10.1111/j.1476-5381.1992.tb14512.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gillespie J. S., Sheng H. A comparison of haemoglobin and erythrocytes as inhibitors of smooth muscle relaxation by the NANC transmitter in the BRP and rat anococcygeus and by EDRF in the rabbit aortic strip. Br J Pharmacol. 1989 Oct;98(2):445–450. doi: 10.1111/j.1476-5381.1989.tb12616.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gillespie J. S., Sheng H. The effects of pyrogallol and hydroquinone on the response to NANC nerve stimulation in the rat anococcygeus and the bovine retractor penis muscles. Br J Pharmacol. 1990 Jan;99(1):194–196. doi: 10.1111/j.1476-5381.1990.tb14677.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gillespie J. S. The rat anococcygeus muscle and its response to nerve stimulation and to some drugs. Br J Pharmacol. 1972 Jul;45(3):404–416. doi: 10.1111/j.1476-5381.1972.tb08097.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hobbs A. J., Tucker J. F., Gibson A. Differentiation by hydroquinone of relaxations induced by exogenous and endogenous nitrates in non-vascular smooth muscle: role of superoxide anions. Br J Pharmacol. 1991 Nov;104(3):645–650. doi: 10.1111/j.1476-5381.1991.tb12483.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jenkinson K. M., Reid J. J., Rand M. J. Hydroxocobalamin and haemoglobin differentiate between exogenous and neuronal nitric oxide in the rat gastric fundus. Eur J Pharmacol. 1995 Mar 6;275(2):145–152. doi: 10.1016/0014-2999(94)00762-v. [DOI] [PubMed] [Google Scholar]
  14. Knudsen M. A., Svane D., Tøttrup A. Action profiles of nitric oxide, S-nitroso-L-cysteine, SNP, and NANC responses in opossum lower esophageal sphincter. Am J Physiol. 1992 May;262(5 Pt 1):G840–G846. doi: 10.1152/ajpgi.1992.262.5.G840. [DOI] [PubMed] [Google Scholar]
  15. Li C. G., Rand M. J. Effects of hydroxocobalamin and haemoglobin on no-mediated relaxations in the rat anococcygeus muscle. Clin Exp Pharmacol Physiol. 1993 Oct;20(10):633–640. doi: 10.1111/j.1440-1681.1993.tb01645.x. [DOI] [PubMed] [Google Scholar]
  16. Li C. G., Rand M. J. Evidence for a role of nitric oxide in the neurotransmitter system mediating relaxation of the rat anococcygeus muscle. Clin Exp Pharmacol Physiol. 1989 Dec;16(12):933–938. doi: 10.1111/j.1440-1681.1989.tb02404.x. [DOI] [PubMed] [Google Scholar]
  17. Li C. G., Rand M. J. Nitric oxide and vasoactive intestinal polypeptide mediate non-adrenergic, non-cholinergic inhibitory transmission to smooth muscle of the rat gastric fundus. Eur J Pharmacol. 1990 Dec 4;191(3):303–309. doi: 10.1016/0014-2999(90)94162-q. [DOI] [PubMed] [Google Scholar]
  18. Liu X. R., Gillespie J. S., Gibson I. F., Martin W. Effects of NG-substituted analogues of L-arginine on NANC relaxation of the rat anococcygeus and bovine retractor penis muscles and the bovine penile artery. Br J Pharmacol. 1991 Sep;104(1):53–58. doi: 10.1111/j.1476-5381.1991.tb12384.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Malinski T., Taha Z., Grunfeld S., Patton S., Kapturczak M., Tomboulian P. Diffusion of nitric oxide in the aorta wall monitored in situ by porphyrinic microsensors. Biochem Biophys Res Commun. 1993 Jun 30;193(3):1076–1082. doi: 10.1006/bbrc.1993.1735. [DOI] [PubMed] [Google Scholar]
  20. Martin W., McAllister K. H., Paisley K. NANC neurotransmission in the bovine retractor penis muscle is blocked by superoxide anion following inhibition of superoxide dismutase with diethyldithiocarbamate. Neuropharmacology. 1994 Nov;33(11):1293–1301. doi: 10.1016/0028-3908(94)90029-9. [DOI] [PubMed] [Google Scholar]
  21. Mayer B., Klatt P., Böhme E., Schmidt K. Regulation of neuronal nitric oxide and cyclic GMP formation by Ca2+. J Neurochem. 1992 Dec;59(6):2024–2029. doi: 10.1111/j.1471-4159.1992.tb10090.x. [DOI] [PubMed] [Google Scholar]
  22. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  23. Myers P. R., Minor R. L., Jr, Guerra R., Jr, Bates J. N., Harrison D. G. Vasorelaxant properties of the endothelium-derived relaxing factor more closely resemble S-nitrosocysteine than nitric oxide. Nature. 1990 May 10;345(6271):161–163. doi: 10.1038/345161a0. [DOI] [PubMed] [Google Scholar]
  24. Mülsch A. Nitrogen monoxide transport mechanisms. Arzneimittelforschung. 1994 Mar;44(3A):408–411. [PubMed] [Google Scholar]
  25. Rajanayagam M. A., Li C. G., Rand M. J. Differential effects of hydroxocobalamin on NO-mediated relaxations in rat aorta and anococcygeus muscle. Br J Pharmacol. 1993 Jan;108(1):3–5. doi: 10.1111/j.1476-5381.1993.tb13429.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rand M. J., Li C. G. Differential effects of hydroxocobalamin on relaxations induced by nitrosothiols in rat aorta and anococcygeus muscle. Eur J Pharmacol. 1993 Sep 14;241(2-3):249–254. doi: 10.1016/0014-2999(93)90210-9. [DOI] [PubMed] [Google Scholar]
  27. Rand M. J., Li C. G. Nitric oxide as a neurotransmitter in peripheral nerves: nature of transmitter and mechanism of transmission. Annu Rev Physiol. 1995;57:659–682. doi: 10.1146/annurev.ph.57.030195.003303. [DOI] [PubMed] [Google Scholar]
  28. Rengasamy A., Johns R. A. Regulation of nitric oxide synthase by nitric oxide. Mol Pharmacol. 1993 Jul;44(1):124–128. [PubMed] [Google Scholar]
  29. Rogers N. E., Ignarro L. J. Constitutive nitric oxide synthase from cerebellum is reversibly inhibited by nitric oxide formed from L-arginine. Biochem Biophys Res Commun. 1992 Nov 30;189(1):242–249. doi: 10.1016/0006-291x(92)91550-a. [DOI] [PubMed] [Google Scholar]
  30. Tsunoda R., Okumura K., Ishizaka H., Matsunaga T., Tabuchi T., Yasue H., Akaike T., Sato K., Maeda H. Vasodilator effect of carboxy-2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl in the coronary circulation: in vivo and in vitro studies. Eur J Pharmacol. 1994 Sep 1;262(1-2):55–63. doi: 10.1016/0014-2999(94)90028-0. [DOI] [PubMed] [Google Scholar]
  31. Vedernikov Y. P., Mordvintcev P. I., Malenkova I. V., Vanin A. F. Similarity between the vasorelaxing activity of dinitrosyl iron cysteine complexes and endothelium-derived relaxing factor. Eur J Pharmacol. 1992 Feb 18;211(3):313–317. doi: 10.1016/0014-2999(92)90386-i. [DOI] [PubMed] [Google Scholar]
  32. Wood J., Garthwaite J. Models of the diffusional spread of nitric oxide: implications for neural nitric oxide signalling and its pharmacological properties. Neuropharmacology. 1994 Nov;33(11):1235–1244. doi: 10.1016/0028-3908(94)90022-1. [DOI] [PubMed] [Google Scholar]
  33. Yoshida K., Akaike T., Doi T., Sato K., Ijiri S., Suga M., Ando M., Maeda H. Pronounced enhancement of .NO-dependent antimicrobial action by an .NO-oxidizing agent, imidazolineoxyl N-oxide. Infect Immun. 1993 Aug;61(8):3552–3555. doi: 10.1128/iai.61.8.3552-3555.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Yoshida M., Akaike T., Wada Y., Sato K., Ikeda K., Ueda S., Maeda H. Therapeutic effects of imidazolineoxyl N-oxide against endotoxin shock through its direct nitric oxide-scavenging activity. Biochem Biophys Res Commun. 1994 Jul 29;202(2):923–930. doi: 10.1006/bbrc.1994.2018. [DOI] [PubMed] [Google Scholar]

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