Summary
The nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), produced large endothelium-dependent contractions in isolated segments of the porcine splenic artery, equivalent to approximately 30% of the maximum responses to 5-hydroxytyptamine (5-HT). These responses were inhibited by 1mM L-arginine, but not by either 1mM D-arginine or the superoxide anion scavenger, superoxide dismutase. However, L-NAME-induced contractions were markedly inhibited by the cyclooxygenase inhibitor, flurbiprofen, and the lipoxygenase inhibitor, 2,3,5-tri-methyl-6-(12-hydroxy-5,10-dodecadiynyl)1,4-benzoquinone (AA-861). The combined cyclooxygenase and lipoxygenase inhibitor 3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline (BW 755C) abolished L-NAME-induced contractions. These findings suggest that suppression of endothelial nitric oxide synthase in the porcine isolated splenic artery results in activation of arachidonic metabolism and production of vasoconstrictor eicosanoids.
References
Cocks TM, Angus JA (1991) Evidence that contraction of isolated arteries by L-NMMA and NOLA are not due to inhibition of basal EDRF release. J Cardiovasc Pharmacol 17 [Suppl 3]:S159-S164
Cocks TM, Malta E, King SJ, Woods R, Angus JA (1991) Oxyhaemoglobin increases the production of endothelin-1 by endothelial cells in culture. Eur J Pharmacol 196:177–182
Dusting GJ, MacDonald PS (1990) Prostacyclin and vascular function: implication for hypertension and atherosclerosis. Pharmacol Ther 48:323–344
Gardiner SM, Bennett T (1993) Endothelial-derived relaxing factors: focus on nitric oxide. In: Edvinsson L, Uddman R (eds) In: Vascular innervation and receptor mechanism: new perspectives. Academic Press London, pp 41–84
Gold ME, Fukoto JM, Ignarro LJ (1990) Structural analogs of L- arginine cause endothelium-dependent and endothelium-independent, nitric oxide-mediated cyclic GMP formation and vasodilatation, and cause vasoconstriction associated with decreased cyclic GMP formation. Eur J Pharmacol 183:1610–1611
Higgs GA, Flower RJ, Vane JR (1979) A new approach to anti-inflammatory drugs. Biochem Pharmacol 28:1959–1961
Klabunde RE, Ritger RC, Helgrem MC (1991) Cardiovascular actions of inhibitors of endothelial-derived relaxing factor (nitric oxide) formation/release in anaesthetized dogs. Eur J Pharmacol 199:51–59
Kukreja RC, Kontos HA, Hess ML, Ellis EF (1986) PGH synthase and lipoxygenase generate superoxide in the presence of NADH and NADPH. Circ Res 59:612–619
Kutusic ZS, Vanhoutte PM (1989) Superoxide anion is an endothelium-derived contracting factor. Am J Physiol 257:H33-H37
Mülsch A, Busse R (1990) NG-nitro-L-arginine (N5-[imino-(nitro-amino)methyl]-L-ornithine) impairs endothelium-dependent dilations by inhibiting cytosolic nitric oxide synthesis from L-arginine. Naunyn Schmiedeberg's Arch Pharmacol 341:143–147
Nishizawa EE, Wynalda DJ, Suydam DE, Molony BA (1973) Flurbiprofen, a new potent inhibitor of platelet aggregation. Thromb Res 3:577–588
Rees DD, Palmer RMJ, Hodson HF, Moncada S (1989) A specific inhibitor of nitric oxide formation from L-arginine attenuates endothelium-dependent relaxations. Br J Pharmacol 96:418–424
Rees DD, Palmer RMJ, Schulz R, Hodson HF, Moncada S (1990) Characterization of three inhibitors of endothelial nitric oxide synthase in vivo and in vitro. Br J Pharmacol 101:746–752
Rosenblum WI, Nishimura H, Nelson GH (1992) L-NMMA in brain microcirculation is inhibited by blockade of cyclooxygenase and by superoxide dismutase. Am J Physiol 262:H1343-H1349
Trezise DJ, Drew GM, and Weston AH (1992) Analysis of the depressant effect of the endothelium on contractions of rabbit isolated basilar artery to 5-hydroxytryptamine. Br J Pharmacol 106: 587–593
Yoshimoto T, Yokayama C, Ochi K, Yamamoto S, Maki Y, Ashida Y, Tearo, Shiraishi M (1982) 2,3,5-tri-methyl-6-(12-hydroxy-5,10-dodecadiynyl)1,4-benzoquinone (AA 861), a selective inhibitor of the 5-lipoxygenase reaction and biosynthesis of slow-reacting substance of anaphylaxis. Biochim Biophys Acta 713:470–473
Wright CE, Rees DD, Moncada S (1992) Protective and pathological roles of nitric oxide in endotoxin shock. Cardiovasc Res 26:48–57
Author information
Authors and Affiliations
Additional information
Correspondence to V. G. Wilson at the above address
Rights and permissions
About this article
Cite this article
Lot, T.Y., Stark, G. & Wilson, V.G. Endothelium-dependent contractions to NG-nitro-L-arginine methyl ester in the porcine isolated splenic artery are sensitive to cyclooxygenase and lipoxygenase inhibitors. Naunyn-Schmiedeberg's Arch Pharmacol 347, 115–118 (1993). https://doi.org/10.1007/BF00168782
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00168782