Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1992 Oct;107(2):476–480. doi: 10.1111/j.1476-5381.1992.tb12770.x

NG-hydroxy-L-arginine prevents the haemodynamic effects of nitric oxide synthesis inhibition in the anaesthetized rat.

C E Walder 1, C Thiemermann 1, J R Vane 1
PMCID: PMC1907884  PMID: 1422593

Abstract

1. We have investigated the effects of L-hydroxy-L-arginine (L-HOArg), an intermediate in the biosynthesis of nitric oxide (NO) from L-arginine (L-Arg), on the haemodynamic effects (systemic blood pressure and renal blood flow) of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in the anaesthetized rat. 2. L-Arg or L-HOArg (3 mg kg-1 min-1), but not D-arginine (D-Arg) or NG-hydroxy-D-arginine (D-HOArg), elicited a slight but significant increase in total renal blood flow (RBF) of 11 +/- 2% and 11 +/- 1%. Since mean arterial blood pressure (MAP) did not change this dose of L-Arg or L-HOArg resulted in a reduced renal vascular resistance (RVR) of the same magnitude. 3. Bolus injections of L-NAME, at 0.3 or 1 mg kg-1 i.v., produced a significant fall in RBF of 11 +/- 2% and 32 +/- 5% and an increase in MAP of 7 +/- 3 mmHg and 22 +/- 5 mmHg, respectively. Consequently, RVR was elevated by 21 +/- 5% and 52 +/- 10%. 4. L-Arg or L-HOArg (3 mg kg-1 min-1) reduced the L-NAME-induced (0.3 or 1 mg kg-1) falls in RBF and increases in RVR by more than 65%. Neither D-Arg nor D-HOArg (3 mg kg-1 min-1) had any significant effect on the changes in RBF or RVR induced by L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
480

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barbul A. Arginine: biochemistry, physiology, and therapeutic implications. JPEN J Parenter Enteral Nutr. 1986 Mar-Apr;10(2):227–238. doi: 10.1177/0148607186010002227. [DOI] [PubMed] [Google Scholar]
  2. Bhardwaj R., Moore P. K. The effect of arginine and nitric oxide on resistance blood vessels of the perfused rat kidney. Br J Pharmacol. 1989 Jul;97(3):739–744. doi: 10.1111/j.1476-5381.1989.tb12011.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Billiar T. R., Curran R. D., Stuehr D. J., West M. A., Bentz B. G., Simmons R. L. An L-arginine-dependent mechanism mediates Kupffer cell inhibition of hepatocyte protein synthesis in vitro. J Exp Med. 1989 Apr 1;169(4):1467–1472. doi: 10.1084/jem.169.4.1467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Brezis M., Silva P., Epstein F. H. Amino acids induce renal vasodilatation in isolated perfused kidney: coupling to oxidative metabolism. Am J Physiol. 1984 Dec;247(6 Pt 2):H999–1004. doi: 10.1152/ajpheart.1984.247.6.H999. [DOI] [PubMed] [Google Scholar]
  6. Busse R., Mülsch A. Induction of nitric oxide synthase by cytokines in vascular smooth muscle cells. FEBS Lett. 1990 Nov 26;275(1-2):87–90. doi: 10.1016/0014-5793(90)81445-t. [DOI] [PubMed] [Google Scholar]
  7. Curran R. D., Billiar T. R., Stuehr D. J., Hofmann K., Simmons R. L. Hepatocytes produce nitrogen oxides from L-arginine in response to inflammatory products of Kupffer cells. J Exp Med. 1989 Nov 1;170(5):1769–1774. doi: 10.1084/jem.170.5.1769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Drexler H., Zeiher A. M., Meinzer K., Just H. Correction of endothelial dysfunction in coronary microcirculation of hypercholesterolaemic patients by L-arginine. Lancet. 1991 Dec 21;338(8782-8783):1546–1550. doi: 10.1016/0140-6736(91)92372-9. [DOI] [PubMed] [Google Scholar]
  9. Dwyer M. A., Bredt D. S., Snyder S. H. Nitric oxide synthase: irreversible inhibition by L-NG-nitroarginine in brain in vitro and in vivo. Biochem Biophys Res Commun. 1991 May 15;176(3):1136–1141. doi: 10.1016/0006-291x(91)90403-t. [DOI] [PubMed] [Google Scholar]
  10. Epstein F. H., Brosnan J. T., Tange J. D., Ross B. D. Improved function with amino acids in the isolated perfused kidney. Am J Physiol. 1982 Sep;243(3):F284–F292. doi: 10.1152/ajprenal.1982.243.3.F284. [DOI] [PubMed] [Google Scholar]
  11. Featherston W. R., Rogers Q. R., Freedland R. A. Relative importance of kidney and liver in synthesis of arginine by the rat. Am J Physiol. 1973 Jan;224(1):127–129. doi: 10.1152/ajplegacy.1973.224.1.127. [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., Kemp P. A., Bennett T. Regional and cardiac haemodynamic effects of NG-nitro-L-arginine methyl ester in conscious, Long Evans rats. Br J Pharmacol. 1990 Nov;101(3):625–631. doi: 10.1111/j.1476-5381.1990.tb14131.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gold M. E., Bush P. A., Ignarro L. J. Depletion of arterial L-arginine causes reversible tolerance to endothelium-dependent relaxation. Biochem Biophys Res Commun. 1989 Oct 31;164(2):714–721. doi: 10.1016/0006-291x(89)91518-0. [DOI] [PubMed] [Google Scholar]
  15. Hecker M., Mitchell J. A., Harris H. J., Katsura M., Thiemermann C., Vane J. R. Endothelial cells metabolize NG-monomethyl-L-arginine to L-citrulline and subsequently to L-arginine. Biochem Biophys Res Commun. 1990 Mar 30;167(3):1037–1043. doi: 10.1016/0006-291x(90)90627-y. [DOI] [PubMed] [Google Scholar]
  16. Ishii K., Chang B., Kerwin J. F., Jr, Huang Z. J., Murad F. N omega-nitro-L-arginine: a potent inhibitor of endothelium-derived relaxing factor formation. Eur J Pharmacol. 1990 Feb 6;176(2):219–223. doi: 10.1016/0014-2999(90)90531-a. [DOI] [PubMed] [Google Scholar]
  17. Linder L., Kiowski W., Bühler F. R., Lüscher T. F. Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo. Blunted response in essential hypertension. Circulation. 1990 Jun;81(6):1762–1767. doi: 10.1161/01.cir.81.6.1762. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Moore P. K., al-Swayeh O. A., Chong N. W., Evans R. A., Gibson A. L-NG-nitro arginine (L-NOARG), a novel, L-arginine-reversible inhibitor of endothelium-dependent vasodilatation in vitro. Br J Pharmacol. 1990 Feb;99(2):408–412. doi: 10.1111/j.1476-5381.1990.tb14717.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. Radermacher J., Klanke B., Kastner S., Haake G., Schurek H. J., Stolte H. F., Frölich J. C. Effect of arginine depletion on glomerular and tubular kidney function: studies in isolated perfused rat kidneys. Am J Physiol. 1991 Nov;261(5 Pt 2):F779–F786. doi: 10.1152/ajprenal.1991.261.5.F779. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. Walder C. E., Thiemermann C., Vane J. R. The involvement of endothelium-derived relaxing factor in the regulation of renal cortical blood flow in the rat. Br J Pharmacol. 1991 Apr;102(4):967–973. doi: 10.1111/j.1476-5381.1991.tb12285.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wallace G. C., Gulati P., Fukuto J. M. N omega-hydroxy-L-arginine: a novel arginine analog capable of causing vasorelaxation in bovine intrapulmonary artery. Biochem Biophys Res Commun. 1991 Apr 15;176(1):528–534. doi: 10.1016/0006-291x(91)90957-9. [DOI] [PubMed] [Google Scholar]
  27. 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]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES