• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. May 1989; 86(9): 3375–3378.
PMCID: PMC287135

Role of endothelium-derived nitric oxide in the regulation of blood pressure.


The role of endothelium-derived nitric oxide in the regulation of blood pressure in the anesthetized rabbit was studied with N omega-monomethyl-L-arginine (L-NMMA), a specific inhibitor of its formation from L-arginine. L-NMMA (3-100 mg.kg-1), but not its D-enantiomer, induced a dose-dependent long-lasting (15-90 min) increase in mean systemic arterial blood pressure. L-NMMA (100 mg.kg-1) also inhibited significantly the hypotensive action of acetylcholine, without affecting that of glyceryl trinitrate. Both these actions of L-NMMA were reversed by L-arginine (300 mg.kg-1), but not by D-arginine (300 mg.kg-1), indomethacin (1 mg.kg-1), prazosin (0.3 mg.kg-1), or by vagotomy. The effects of L-NMMA in vivo were associated with a significant inhibition of the release of nitric oxide from perfused aortic segments ex vivo. This inhibition was reversed by infusing L-arginine through the aortic segments. These results indicate that nitric oxide formation from L-arginine by the vascular endothelium plays a role in the regulation of blood pressure and in the hypotensive actions of acetylcholine.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (708K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. [PubMed]
  • Furchgott RF. The role of endothelium in the responses of vascular smooth muscle to drugs. Annu Rev Pharmacol Toxicol. 1984;24:175–197. [PubMed]
  • Griffith TM, Edwards DH, Lewis MJ, Newby AC, Henderson AH. The nature of endothelium-derived vascular relaxant factor. Nature. 1984 Apr 12;308(5960):645–647. [PubMed]
  • Rees DD, Palmer RM, Hodson HF, Moncada S. A specific inhibitor of nitric oxide formation from L-arginine attenuates endothelium-dependent relaxation. Br J Pharmacol. 1989 Feb;96(2):418–424. [PMC free article] [PubMed]
  • Holtz J, Förstermann U, Pohl U, Giesler M, Bassenge E. Flow-dependent, endothelium-mediated dilation of epicardial coronary arteries in conscious dogs: effects of cyclooxygenase inhibition. J Cardiovasc Pharmacol. 1984 Nov-Dec;6(6):1161–1169. [PubMed]
  • Angus JA, Campbell GR, Cocks TM, Manderson JA. Vasodilatation by acetylcholine is endothelium-dependent: a study by sonomicrometry in canine femoral artery in vivo. J Physiol. 1983 Nov;344:209–222. [PMC free article] [PubMed]
  • Rosenblum WI, Nelson GH, Povlishock JT. Laser-induced endothelial damage inhibits endothelium-dependent relaxation in the cerebral microcirculation of the mouse. Circ Res. 1987 Feb;60(2):169–176. [PubMed]
  • Sobey CG, Woodman OL, Dusting GJ. Inhibition of vasodilatation by methylene blue in large and small arteries of the dog hindlimb in vivo. Clin Exp Pharmacol Physiol. 1988 May;15(5):401–410. [PubMed]
  • Dudel C, Förstermann U. Gossypol attenuates selectively the blood pressure lowering effect of endothelium-dependent vasodilators in the rabbit in vivo. Eur J Pharmacol. 1988 Jan 12;145(2):217–221. [PubMed]
  • Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. [PubMed]
  • Radomski MW, Palmer RM, Moncada S. Comparative pharmacology of endothelium-derived relaxing factor, nitric oxide and prostacyclin in platelets. Br J Pharmacol. 1987 Sep;92(1):181–187. [PMC free article] [PubMed]
  • Radomski MW, Palmer RM, Moncada S. The role of nitric oxide and cGMP in platelet adhesion to vascular endothelium. Biochem Biophys Res Commun. 1987 Nov 13;148(3):1482–1489. [PubMed]
  • Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9265–9269. [PMC free article] [PubMed]
  • Kelm M, Feelisch M, Spahr R, Piper HM, Noack E, Schrader J. Quantitative and kinetic characterization of nitric oxide and EDRF released from cultured endothelial cells. Biochem Biophys Res Commun. 1988 Jul 15;154(1):236–244. [PubMed]
  • Palmer RM, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 1988 Jun 16;333(6174):664–666. [PubMed]
  • Schmidt HH, Nau H, Wittfoht W, Gerlach J, Prescher KE, Klein MM, Niroomand F, Böhme E. Arginine is a physiological precursor of endothelium-derived nitric oxide. Eur J Pharmacol. 1988 Sep 13;154(2):213–216. [PubMed]
  • Palmer RM, Rees DD, Ashton DS, 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. [PubMed]
  • Sakuma I, Stuehr DJ, Gross SS, Nathan C, Levi R. Identification of arginine as a precursor of endothelium-derived relaxing factor. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8664–8667. [PMC free article] [PubMed]
  • Patthy A, Bajusz S, Patthy L. Preparation and characterization of Ng-mono-, di- and trimethylated arginines. Acta Biochim Biophys Acad Sci Hung. 1977;12(3):191–196. [PubMed]
  • Amezcua JL, Dusting GJ, Palmer RM, Moncada S. Acetylcholine induces vasodilatation in the rabbit isolated heart through the release of nitric oxide, the endogenous nitrovasodilator. Br J Pharmacol. 1988 Nov;95(3):830–834. [PMC free article] [PubMed]
  • Koulu M, Lappalainen J, Pesonen U, Hietala J, Syvälahti E. Chronic treatment with SCH 23390, a selective dopamine D-1 receptor antagonist, decreases dopamine metabolism in rat caudate nucleus. Eur J Pharmacol. 1988 Oct 18;155(3):313–316. [PubMed]
  • Thomas G, Mostaghim R, Ramwell PW. Endothelium dependent vascular relaxation by arginine containing polypeptides. Biochem Biophys Res Commun. 1986 Dec 15;141(2):446–451. [PubMed]
  • Lüscher TF, Diederich D, Weber E, Vanhoutte PM, Bühler FR. Endothelium-dependent responses in carotid and renal arteries of normotensive and hypertensive rats. Hypertension. 1988 Jun;11(6 Pt 2):573–578. [PubMed]
  • Winquist RJ, Bunting PB, Baskin EP, Wallace AA. Decreased endothelium-dependent relaxation in New Zealand genetic hypertensive rats. J Hypertens. 1984 Oct;2(5):541–545. [PubMed]
  • Otsuka Y, DiPiero A, Hirt E, Brennaman B, Lockette W. Vascular relaxation and cGMP in hypertension. Am J Physiol. 1988 Jan;254(1 Pt 2):H163–H169. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...