Skip to main content
SpringerLink
Log in

Acute normovolaemic anaemia prevents ethanol-induced gastric damage in rats through a blood flow related mechanism

  • Original Articles
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

The aim of the study was to assess whether changes in gastric mucosal blood flow induced by acute normovolaemic anaemia influence the susceptibility of the gastric mucosa to ethanol-induced damage, and the relationship of these changes with nitric oxide biosynthesis. Acute normovolaemic anaemia, promoted by exchanging 3 ml of blood by a plasma expander, induced a significant increase in gastric mucosal blood flow measured by hydrogen gas clearance, without changes in arterial blood pressure. After intragastric 60% ethanol administration, gastric blood flow was still significantly higher in anaemic than in control rats, and this was associated with a lower macroscopic and microscopic gastric damage. Following ethanol administration, anaemic rats pretreated with an inhibitor of nitric oxide biosynthesis (l-NMMA, 50 mg/kg, i.v.) had a lower gastric blood flow and a higher macroscopic gastric damage than anaemic rats without pretreatment. Anaemic rats pretreated with vasopressin also had after ethanol administration a lower gastric blood flow and a higher macroscopic gastric damage. It is concluded that acute normovolaemic anaemia protects the gastric mucosa against damage induced by intragastric ethanol. The inhibition of nitric oxide biosynthesis reverts in part this protective effect, and this seems to be related with the capability of nitric oxide to increase gastric mucosal blood flow, since vasoconstriction by a nitric oxide-independent mechanism causes a similar effect.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Anand IS, Chandrashekhar Y (1993) Reduced inhibition of endothelial-derived relaxing factor causes the hyperdynamic circulation in chronic severe anemia. Med Hypotheses 41:225–228

    Google Scholar 

  • Bath PMW, Hasall DG, Gladwin AM, Palmer RMJ, Martin JF (1991) Nitric oxide and prostacyclin. Divergence of inhibitory effects on monocyte chemotaxis and adhesion to endothelium in vitro. Arterioscler Thromb 11:254–260

    Google Scholar 

  • Boughton-Smith NK, Whittle BJR (1988) Inhibition by 16,16-dimethyl PGE2 of ethanol-induced gastric mucosal damage and leukotriene B4 and C4 formation. Prostglandins 35:945–957

    Google Scholar 

  • Dintenfass L (1971) Blood-microrheology-viscosity factors in blood flow, ischemia, and thrombosis. Apple-Centruy-Crofts, New York

    Google Scholar 

  • Fowler NO, Holmes JC (1975) Blood viscosity and cardiac output in acute experimental anemia. J Appl Physiol 39:453–456

    Google Scholar 

  • Gaboury J, Woodman RC, Granger DN, Reinhardt P, Kubes P (1993) Nitric oxide prevents leukocyte adherence: role of superoxide. Am J Physiol 265:H862-H867

    Google Scholar 

  • Guth PH, Paulsen G, Nagata H (1984) Histologic and microcirculatory changes in alcohol-induced gastric lesions in the rat: effect of prostaglandin cytoprotection. Gastroenterology 87:1083–1090

    Google Scholar 

  • Jacobson ED (1992) Circulatory mechanisms of gastric mucosal damage and protection. Gastroenterology 102:1788–1800

    Google Scholar 

  • Karmeli F, Eliakim R, Okon E, Rachmilewitz D (1991) Gastric mucosal damage by ethanol is mediated by substance P and prevented by ketotifen, a mast cell stabilizer. Gastroenterology 100:1206–1216

    Google Scholar 

  • Kourembanas S, McQuillan LP, Leung GK, Faller DV (1993) Nitric oxide regulates the expression of vasoconstrictors and growth factors by vascular endothelium and both normoxia and hypoxia. J Clin Invest 92:99–104

    Google Scholar 

  • Kravetz D, Arderiu MT, Bosch J, Piera C, Setoain J, Rodés J (1987) Increased plasma volume in two models of portal hypertension in the rat: cirrhosis of the liver and partial portal vein ligation. Rev Esp Fisiol 43:179–184

    Google Scholar 

  • Kubes P, Suzuki M, Granger DN (1991) Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci USA 88:4651–4655

    Google Scholar 

  • Kubes P (1992) Polymorphonuclear leukocyte-endothelium interactions: a role for pro-inflammatory and anti-inflammatory molecules. Can J Physiol 71:88–97

    Google Scholar 

  • Lambrecht N, Trautmann M, Korojkiewicz R, Liszkay M, Peskar BM (1993) Role of eicosanoids, nitric oxide, and afferent neurones in antacid induced protection in the rat stomach. Gut 34:329–337

    Google Scholar 

  • Leung FW, Guth PH, Scremin OU, Golanska E, Kauffman G Jr. (1984) Regional gastric mucosal blood flow measurements by hydrogen gas clearance in the anesthetized rat and rabbit. Gastroenterology 87:28–36

    Google Scholar 

  • Leung FW, Itoh H, Hirabayashi K, Guth PH (1985) Role of blood flow in gastric and duodenal mucosal injury in the rat. Gastroenterology 88:281–289

    Google Scholar 

  • Lippe IT, Holzer P (1992) Participation of endothelium-derived nitric oxide but not prostacyclin in the gastric mucosal hyperemia due to acid back-diffusion. Br J Pharmacol 105:708–714

    Google Scholar 

  • MacNaughton WK, Cirino G, Wallace JL (1989) Endothelium-derived relaxing factor (nitric oxide) has protective actions in the stomach. Life Sci 45:1869–1876

    Google Scholar 

  • Masuda E, Kawano S, Nagano K, Tsuji S, Ishigami Y, Tsujii M, Hayashi N, Fusamoto H, Kamada T (1992) Effect of intravascular ethanol on modulation of gastric mucosal integrity: possible role of endothelin-1. Am J Physiol 262:G785-G790

    Google Scholar 

  • Murray JF, Escobar E, Rapaport E (1969) Effects of blood viscosity on hemodynamic response in acute normovolemic anemia. Am J Physiol 216:638–642

    Google Scholar 

  • Panés J, Casadevall M, Piqué JM, Bosch J, Whittle BJR, Terés J (1992) Effects of acute normovolemic anemia on gastric mucosal blood flow in rats: role of nitric oxide. Gastroenterology 103:407–413

    Google Scholar 

  • Pihan G, Majzoubi D, Haudenschild C, Trier JS, Szabo S (1986) Early microcirculatory stasis in acute gastric mucosal injury in the rat and prevention by 16,16-dimethyl prostaglandin E2 or sodium thiosulfate. Gastroenterology 91:1415–1426

    Google Scholar 

  • Peskar BM, Lange K, Hoppe U, Peskar BA (1986) Ethanol stimulates formation of leukotriene C4 in rat gastric mucosa. Prostaglandins 31:283–293

    Google Scholar 

  • Peskar BM, Responsek M, Müller KM, Peskar BA (1991) A role of nitric oxide in capsaicin-induced gastroprotection. Eur J Pharmacol 198:113–114

    Google Scholar 

  • Piqué JM, Leung FW, Tan HW, Livingston E, Scremin OU, Guth PH (1988) Gastric mucosal blood flow response to stimulationa and inhibition of gastric acid secretion. Gastroenterology 95:642–650

    Google Scholar 

  • Piqué JM, Whittle BJR, Esplugues JV (1989) The vasodilator role of endogenous nitric oxide in the rat gastric microcirculation. Eur J Pharmacol 174:293–296

    Google Scholar 

  • Piqué JM, Esplugues JV, Whittle BJR (1992) Endogenous nitric oxide as a mediator of gastric mucosal vasodilatation during acid secretion. Gastroenterology 102:168–174

    Google Scholar 

  • Pizcueta MP, Pique JM, Bosch J, Whittle BJR, Moncada S (1992) Effects of inhibiting nitric oxide biosynthesis on the systemic and splanchnic circulation of rats with portal hypertension. Br J Pharmacol 105:184–190

    Google Scholar 

  • Quintero E, Guth PH (1992) Renal failure increases gastric mucosal blood flow and acid secretion in rats: role of endothelium-derived nitric oxide. Am J Physiol 263:G75-G80

    Google Scholar 

  • Radomski MW, Palmer RMJ, Moncada S (1987) Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium. Lancet 11:1057–1058

    Google Scholar 

  • Radomski MW, Palmer RMJ, Moncada S (1990) An L-arginine/nitric oxide pathway present in human platelets regulates aggregation. Proc Natl Acad Sci USA 87:5193–5197

    Google Scholar 

  • Rooney MW, Hirsch LJ, Mathru M (1993) Hemodilution with oxyhemoglobin. Mechanism of oxygen delivery and its superaugmentation with a nitric oxide donor (sodium nitroprusside). Anesthesiology 79:60–72

    Google Scholar 

  • Rosberg B, Wulff K (1979) Regional blood flow in normovolaemic and hypovolaemic haemodilution. An experimental study. Br J Anaesth 51:423–430

    Google Scholar 

  • Szelenyi I, Brune K (1988) Possible role of oxygen free radicals in ethanol-induced gastric mucosal damage. Dig Dis Sci 33:865–871

    Google Scholar 

  • Varat MA, Adolph RJ, Fowler NO (1972) The cardiovascular effects of anemia. Am Heart J 83:415–424

    Google Scholar 

  • Wallace JL, Beck PL, Morris GP (1988) Is there a role for leukotrienes mediators of ethanol-induced gastric mucosal damage? Am J Physiol 254-G117-G123

    Google Scholar 

  • Whittle BJR, Lopez-Belmonte J, Moncada S (1990) Regulation of gastric mucosal integrity by endogenous nitric oxide: interaction with prostanoids and sensory neuropeptides. Br J Pharmacol 99:607–611

    Google Scholar 

  • Whittle BJR (1993) Neuronal and endothelium-derived mediators in the modulation of the gastric microcirculation: integrity in the balance. Br J Pharmacol 110:3–17

    Google Scholar 

  • Yoneda M, Taché Y (1992) Central thyrotropin-releasing factor analog prevents ethanol-induced gastric damage through prostaglandins in rats. Gastroenterology 102:1568–1574

    Google Scholar 

  • Yonei Y, Wayland H, Guth PH (1988) Role of arachidonic acid metabolites in ethanol vasoaction in rat gastric submucosa. Am J Physiol 55:G731-G737

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Gastroenterology Department, Hospital Clínic, University of Barcelona, Spain

    Maria Casadevall, Josep M. Piqué, Isabel Cirera & Josep Terés

  2. Department of Pharmacology, University of Valencia, Spain

    M. Dolores Barrachina

Authors
  1. Maria Casadevall
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Josep M. Piqué
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Isabel Cirera
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Dolores Barrachina
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Josep Terés
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Casadevall, M., Piqué, J.M., Cirera, I. et al. Acute normovolaemic anaemia prevents ethanol-induced gastric damage in rats through a blood flow related mechanism. Naunyn-Schmiedeberg's Arch Pharmacol 350, 569–574 (1994). https://doi.org/10.1007/BF00173028

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00173028

Key words

Search

Navigation