Abstract
Endotoxin shock was induced in 31 anaesthetized pigs by infusion of 5 μg/kg of Escbeicbia coli endotoxin (LPS) over 60 min into the superior mesenteric artery. Fifteen of these pigs died within 30 min of the start of LPS infusion whereas the remaining 16 survived the experimental period of 2 h. In a group of nine pigs indomethacin (2 mg/kg, i.v.)was inected 20–25 rain after the start of LPS infusion at which time mean arterial blood pressure (MABP) had decreased below 40 mmHg indicating imminent death. Indomethacin immediately reversed the hypotension. In another group of five pigs, NG-nitro L-arginine-methyl ester (L-NAME, 1 and 3 mg/kg)was iniected 10 and 5 min, respectively, before the expected death without any beneficial effect on the hypotension. Three rain after the last dose of L-NAME, indomethacin (2 mg/kg, i.v.) was iniected. In three animals the hypotension was reserved by indomethacin, although this beneficial effect was delayed in comparison with the LP-Streated group not receiving L-NAME. Four pigs were pretreated with L-NAME, 3 mg/kg, i.v., 10 min prior to LPS infusion. All pretreated animals tended to die within 30 min of the start of the LPS infusion. Five rain before the expected death (20–25 rain after the start of LPS infusion) indomethacin (2 mg/kg) was inected. In three of these animals indomethacin reversed hypotenston and prevented death. Interestingly, this rise in the MABP developed very slowly. These results suggest that the beneficial effect of indomethacin in endotoxin shock might be related partially to interference with nitric oxide, which is not the only factor determining blood pressure levels during endotoxic shock.
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- Abramson S., Korchak H., Ludewig R., Edelson H., Haines K., Levin R. I., Herman R., Rider L., Kimmel S., Weissmann G. Modes of action of aspirin-like drugs. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7227–7231. doi: 10.1073/pnas.82.21.7227. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Balk R. A., Jacobs R. F., Tryka A. F., Walls R. C., Bone R. C. Low dose ibuprofen reverses the hemodynamic alterations of canine endotoxin shock. Crit Care Med. 1988 Nov;16(11):1128–1131. doi: 10.1097/00003246-198811000-00009. [DOI] [PubMed] [Google Scholar]
- Dinarello C. A. The proinflammatory cytokines interleukin-1 and tumor necrosis factor and treatment of the septic shock syndrome. J Infect Dis. 1991 Jun;163(6):1177–1184. doi: 10.1093/infdis/163.6.1177. [DOI] [PubMed] [Google Scholar]
- Finkel M. S., Oddis C. V., Jacob T. D., Watkins S. C., Hattler B. G., Simmons R. L. Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science. 1992 Jul 17;257(5068):387–389. doi: 10.1126/science.1631560. [DOI] [PubMed] [Google Scholar]
- Fletcher J. R., Ramwell P. W. Modification, by aspirin and indomethacin, of the haemodynamic and prostaglandin releasing effects of E. coli endotoxin in the dog. Br J Pharmacol. 1977 Oct;61(2):175–181. doi: 10.1111/j.1476-5381.1977.tb08402.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gardiner S. M., Compton A. M., Kemp P. A., Bennett T. Regional and cardiac haemodynamic responses to glyceryl trinitrate, acetylcholine, bradykinin and endothelin-1 in conscious rats: effects of NG-nitro-L-arginine methyl ester. Br J Pharmacol. 1990 Nov;101(3):632–639. doi: 10.1111/j.1476-5381.1990.tb14132.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hutcheson I. R., Whittle B. J., Boughton-Smith N. K. Role of nitric oxide in maintaining vascular integrity in endotoxin-induced acute intestinal damage in the rat. Br J Pharmacol. 1990 Dec;101(4):815–820. doi: 10.1111/j.1476-5381.1990.tb14163.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kelm M., Schrader J. Control of coronary vascular tone by nitric oxide. Circ Res. 1990 Jun;66(6):1561–1575. doi: 10.1161/01.res.66.6.1561. [DOI] [PubMed] [Google Scholar]
- Kilbourn R. G., Jubran A., Gross S. S., Griffith O. W., Levi R., Adams J., Lodato R. F. Reversal of endotoxin-mediated shock by NG-methyl-L-arginine, an inhibitor of nitric oxide synthesis. Biochem Biophys Res Commun. 1990 Nov 15;172(3):1132–1138. doi: 10.1016/0006-291x(90)91565-a. [DOI] [PubMed] [Google Scholar]
- 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]
- Morrison D. C., Ryan J. L. Endotoxins and disease mechanisms. Annu Rev Med. 1987;38:417–432. doi: 10.1146/annurev.me.38.020187.002221. [DOI] [PubMed] [Google Scholar]
- Mózes T., Wieszt E., Zahajszky T. Role of PGF2 alpha in the superior mesenteric artery-induced shock. J Surg Res. 1989 Dec;47(6):476–481. doi: 10.1016/0022-4804(89)90123-6. [DOI] [PubMed] [Google Scholar]
- Mózes T., Zijlstra F. J., Heiligers J. P., Tak C. J., Ben-Efraim S., Bonta I. L., Saxena P. R. Sequential release of tumour necrosis factor, platelet activating factor and eicosanoids during endotoxin shock in anaesthetized pigs: protective effects of indomethacin. Br J Pharmacol. 1991 Nov;104(3):691–699. doi: 10.1111/j.1476-5381.1991.tb12490.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nava E., Palmer R. M., Moncada S. Inhibition of nitric oxide synthesis in septic shock: how much is beneficial? Lancet. 1991 Dec 21;338(8782-8783):1555–1557. doi: 10.1016/0140-6736(91)92375-c. [DOI] [PubMed] [Google Scholar]
- Petros A., Lamb G., Leone A., Moncada S., Bennett D., Vallance P. Effects of a nitric oxide synthase inhibitor in humans with septic shock. Cardiovasc Res. 1994 Jan;28(1):34–39. doi: 10.1093/cvr/28.1.34. [DOI] [PubMed] [Google Scholar]
- Szabó C., Mitchell J. A., Gross S. S., Thiemermann C., Vane J. R. Nifedipine inhibits the induction of nitric oxide synthase by bacterial lipopolysaccharide. J Pharmacol Exp Ther. 1993 May;265(2):674–680. [PubMed] [Google Scholar]
- Szabó C., Mitchell J. A., Thiemermann C., Vane J. R. Nitric oxide-mediated hyporeactivity to noradrenaline precedes the induction of nitric oxide synthase in endotoxin shock. Br J Pharmacol. 1993 Mar;108(3):786–792. doi: 10.1111/j.1476-5381.1993.tb12879.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thiemermann C., Szabó C., Mitchell J. A., Vane J. R. Vascular hyporeactivity to vasoconstrictor agents and hemodynamic decompensation in hemorrhagic shock is mediated by nitric oxide. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):267–271. doi: 10.1073/pnas.90.1.267. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vadas P., Hay J. B. Involvement of circulating phospholipase A2 in the pathogenesis of the hemodynamic changes in endotoxin shock. Can J Physiol Pharmacol. 1983 Jun;61(6):561–566. doi: 10.1139/y83-086. [DOI] [PubMed] [Google Scholar]
- Vane J. R. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971 Jun 23;231(25):232–235. doi: 10.1038/newbio231232a0. [DOI] [PubMed] [Google Scholar]
- Wang Y. X., Zhou T., Chua T. C., Pang C. C. Effects of inhalation and intravenous anesthetic agents on pressor response to NG-nitro-L-arginine. Eur J Pharmacol. 1991 Jun 6;198(2-3):183–188. doi: 10.1016/0014-2999(91)90619-2. [DOI] [PubMed] [Google Scholar]
- Weitzberg E., Rudehill A., Lundberg J. M. Nitric oxide inhalation attenuates pulmonary hypertension and improves gas exchange in endotoxin shock. Eur J Pharmacol. 1993 Mar 16;233(1):85–94. doi: 10.1016/0014-2999(93)90352-i. [DOI] [PubMed] [Google Scholar]
- Woditsch I., Schrör K. Prostacyclin rather than endogenous nitric oxide is a tissue protective factor in myocardial ischemia. Am J Physiol. 1992 Nov;263(5 Pt 2):H1390–H1396. doi: 10.1152/ajpheart.1992.263.5.H1390. [DOI] [PubMed] [Google Scholar]
- Wright C. E., Rees D. D., Moncada S. Protective and pathological roles of nitric oxide in endotoxin shock. Cardiovasc Res. 1992 Jan;26(1):48–57. doi: 10.1093/cvr/26.1.48. [DOI] [PubMed] [Google Scholar]
- van Gelderen E. M., Den Boer M. O., Saxena P. R. NG-nitro L-arginine methyl ester: systemic and pulmonary haemodynamics, tissue blood flow and arteriovenous shunting in the pig. Naunyn Schmiedebergs Arch Pharmacol. 1993 Oct;348(4):417–423. doi: 10.1007/BF00171342. [DOI] [PubMed] [Google Scholar]
