Skip to main content
SpringerLink
Log in

Effects of PAF on cardiac function and eicosanoid release in the isolated perfused rat heart: comparison between normotensive and spontaneously hypertensive rats

  • Original Contribution
  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Abstract

The aim of this study was (a) in isolated perfused rat heart to characterize the effects of platelet-activating factor (PAF) on coronary flow, ventricular contractility, and eicosanoid release and (b) to determine whether PAF effects are altered in hearts from spontaneously hypertensive rats (SHR). PAF (10−10–10−7 mol) dose-dependently decreased coronary flow and ventricular contractility; concomitantly, coronary effluent concentrations of thromboxane (TX)B2 and prostaglandin F2α (PGF2α) were elevated but not those of prostacyclin. The PAF receptor antagonist WEB 2086 (10−7–10−5 mol/l) concentration-dependently antagonized these PAF effects. In addition, the cyclo-oxygenase inhibitor indomethacin (5×10−5 mol/l) prevented PAF (10−9–10−7 mol) induced eicosanoid release; in the presence of indomethacin PAF caused coronary constriction and ventricular depression only at the highest dose (10−7 mol) but had no effect at 10−9 or 10−8 mol. Moreover, the TXA2 antagonist SQ 29,548 (10−6 mol/l) completely inhibited 10−8 mol PAF induced ventricular depression but did not effect coronary constriction. In SHR PAF (10−9–10−7 mol) evoked decreases in coronary flow and ventricular contractility did not differ from those in normotensive Wistar-Kyoto rats while PAF induced TXA2 and PGF2α release was markedly enhanced. In addition, decreases in coronary flow and ventricular contractility induced by the TXA2 agonist U 46619 (10−7 mol/l) were markedly depressed in SHR. We conclude that in isolated perfused rat heart PAF causes coronary constriction and depression of ventricular function mainly indirectly through released TXA2 and/or PGF2α. Moreover, the fact that in SHR the PAF effects on coronary flow and ventricular function are not altered despite markedly enhanced TXA2 and PGF2α release supports the view that in the SHR the receptors mediating TXA2 and/or PGF2α effects are desensitized.

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

  1. Alloatti G, Montrucchio G, Camussi G (1990) Prostacyclin inhibits the platelet-dependent effects of platelet-activating factor in the rabbit isolated heart. J Cardiovasc Pharmacol 15: 745–751

    Google Scholar 

  2. Benveniste J, Tence M, Varenne P, Bidault J, Boullet C, Polonsky J (1979) Semi-synthesis and proposed structure of platelet-activating factor (PAF): PAF-acether and alkylether analog of lysophosphatidylcholine. CRC Acad Sci 289D: 1037–1040

    Google Scholar 

  3. Berti F, Magni F, Rossoni G, De Angelis L, Galli G (1990) Production and biologic interactions of prostacyclin and platelet-activating factor in acute myocardial ischemia in the perfused rabbit heart. J Cardiovasc Pharmacol 16: 727–732

    Google Scholar 

  4. Blank ML, Lee TC, Cress EA, Molone B, Fitzgerald V, Snyder F (1984) Conversion of 1-alkyl-2-acetyl-sn-glycerols to platelet-activating factor and related phospholipids by rabbit platelets. Biochem Biophys Res Commun 124: 156–163

    Google Scholar 

  5. Braquet P, Paubert-Braquet M, Bessin P, Vergaftig BB (1987) Platelet-activating factor: a potential mediator of shock. Adv Prostaglandin Thromboxane Leukot Res 17: 822

    Google Scholar 

  6. Brodde O-E, Michel MC (1992) Adrenergic receptors and their signal transduction mechanisms in hypertension. J Hypertens 10 (suppl 7): S133-S145

    Google Scholar 

  7. Coleman RA, Smith WL, Narumiya S (1994) VIII. International Union of Pharmacology Classification of Prostanoid Receptors: properties, distribution, and structure of the receptors and their subtypes. Pharmacol Rev 46: 205–229

    Google Scholar 

  8. Delbridge LM, Stewart AG, Goulter CM, Morgan TO, Harris PJ (1994) Platelet-activating factor and WEB-2086 directly modulate rat cardiomyocyte contractility. J Mol Cell Cardiol 26: 185–193

    Google Scholar 

  9. Doebber TW, Wu MS (1988) Platelet-activating factor-induced cellular and pathophysiological responses in the cardiovascular system. Drug Dev Res 12: 151–161

    Google Scholar 

  10. Evangelou AM (1994) Platelet-activating factor (PAF): implications for coronary heart and vascular diseases. Prostaglandins Leukot Essent Fatty Acids 50: 1–28

    Google Scholar 

  11. Felix SB, Baumann G, Raschke P, Maus C, Berdel WE (1990) Cardiovascular reactions and respiratory events during platelet activating factor-induced shock. Basic Res Cardiol 85: 217–226

    Google Scholar 

  12. Felix SB, Baumann G, Ahmad Z, Hashemi T, Niemczyk M, Berdel WE (1990) Effects of platelet-activating factor on myocardial contraction and myocardial relaxation of isolated perfused guinea pig heart. J Cardiovasc Pharmacol 16: 750–756

    Google Scholar 

  13. Felix SB, Steger A, Baumann G, Busch R, Ochsenfeld G, Berdel WE (1990) Platelet-activating factor-induced coronary constriction in the isolated perfused guinea pig heart and antagonistic effects of the PAF antagonist WEB 2086. J Lipid Med 2: 9–20

    Google Scholar 

  14. Giessler C, Panse M, Mentz P, Hellthaler G (1988) An enzyme-linked immunoassay for thromboxane B2 and 6-oxo-PGF1α using peroxidase as label. Biomed Biochim Acta 47 (10/11): 137–139

    Google Scholar 

  15. Heinroth-Hoffmann I, Gießler C, Mest H-J (1992) Relevance of vasoactive mediators for the blood pressure effects of intravenous arachidonic acid injection in rats. Prostaglandins Leukot Essent Fatty Acids 46: 197–201

    Google Scholar 

  16. Ishimitsu T, Uehara Y, Ishii M, Ikeda T, Matsuoka H, Sugimoto T (1989) Alterations of the cardiovascular and renal prostaglandins and thromboxanes system in prehypertensive spontaneously hypertensive rats. Jpn Circ J 53: 307–312

    Google Scholar 

  17. Ishimitsu T, Uehara Y, Iawai J, Sugimoto T, Hirata Y, Matsuoka H, Sugimoto T (1991) Vascular eicosanoids production in experimental hypertensive rats with different mechanisms. Prostaglandins Leukot Essent Fatty Acids 43 (3): 179–184

    Google Scholar 

  18. Janero DR, Burghardt C (1990) Production and release of platelet-activating factor by the injured heart-muscle cell (cardiomyocyte). Res Commun Chem Pathol Pharmacol 67: 201–218

    Google Scholar 

  19. Kamata K, Numazawa T, Kasuya Y (1994) Decrease in vasodilator effects of platelet-activating factor in resistance vessels of spontaneously hypertensive rats. Eur J Pharmacol 259: 321–323

    Google Scholar 

  20. Laurindo FRM, Goldstein RE, Davenport NJ, Ezra D, Feuerstein GZ (1989) Mechanisms of hypertension produced by platelet-activating factor. J Appl Physiol 66: 2681–2690

    Google Scholar 

  21. Man Ryk, Hue W, Kinnaird AAA (1990) Coronary vascular response to platelet-activating factor in the perfused rat heart. J Lipid Med 2: 75–83

    Google Scholar 

  22. Masugi F, Ogihara T, Saeki S, Otsuka A, Kumahara Y (1985) Role of acetyl glyceryl ether phosphorylcholine in blood pressure regulation in rats. Hypertension 7: 742–48

    Google Scholar 

  23. Peplow PV, Mikhailidis DP (1990) Platelet-activating factor (PAF) and its relation to prostaglandins, leukotrienes and other aspects of arachidonate metabolism. Prostaglandins Leukot Essent Fatty Acids 41: 71–82

    Google Scholar 

  24. Piper PJ, Stewart AG (1986) Coronary vasoconstriction in the rat, isolated perfused hearts induced by platelet-activating factor is mediated by leukotrienes C4. Br J Pharmacol 88: 595–605

    Google Scholar 

  25. Piper PJ, Stewart AG (1987) Antagonism of vasoconstriction induced by platelet activating factor in guinea pig perfused hearts by selective platelet-activating factor receptor antagonists. Br J Pharmacol 90: 771–783

    Google Scholar 

  26. Robertson DA, Genovese A, Levi R (1987) Negative inotropic effect of platelet-activating factor on human myocardium: pharmacological study. J Pharmacol Exp Ther 243: 834–839

    Google Scholar 

  27. Sakaguchi K, Morimoto S, Masugi F, Saeki S, Ogihara T, Yamada K, Yamatsu I (1991) Studies on the role of platelet-activating factor in blood pressure regulation. Lipids 26: 1264

    Google Scholar 

  28. Stahl GL, Lefer AM (1987) Mechanisms of platelet-activating factor-induced cardiac depression in the isolated perfused rat heart. Circ Shock 23: 165–177

    Google Scholar 

  29. STahl GL, Lefer DJ, Lefer AM (1987) PAF-acether induced cardiac dysfunction in the isolated perfused guinea pig heart. Naunyn-Schmiedebergs Arch Pharmacol 336: 459–463

    Google Scholar 

  30. Stewart AG, Piper PJ (1988) Platelet-activating factor and the cardiovascular system: involvement in cardiac anaphylaxis. Prog Biochem Pharmacol 22: 132–140

    Google Scholar 

  31. Tanniere M, Rochette I (1987) Direct effects of platelet activating factor (PAF) on cardiac function in isolated guinea pig heart. Drug Development Res 11: 177–186

    Google Scholar 

  32. Taube C, Hoffmann P, Förster W (1982) Enhanced thromboxane production in the aorta of spontaneously hypertensive rats. Prostanglandins Leukot Med 9: 411–414

    Google Scholar 

  33. Viossat I, Chapelat M, Chabrier PE, Braquet P (1989) Effects of platelet activating factor (PAF) and its receptor antagonist BN 52021 on isolated perfused guinea-pig heart. Prostaglandins Leukot Essent Fatty Acids 38: 189–194

    Google Scholar 

  34. Whatley RE, Fennell DF, Kurrus JA, Zimmermann GA, McIntyre TM, Presscott SM (1990) Synthesis of platelet-activating factor by endothelial cells: the role of G proteins. J Biol Chem 265: 15550–15559

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Pharmacology and Toxicology, Martin Luther University Halle-Wittenberg, Magdeburger Straße 4, 06097, Halle, Germany

    C. Giessler, K. Pönicke, C. Steinborn & O. -E. Brodde

Authors
  1. C. Giessler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. Pönicke
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Steinborn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. O. -E. Brodde
    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

Giessler, C., Pönicke, K., Steinborn, C. et al. Effects of PAF on cardiac function and eicosanoid release in the isolated perfused rat heart: comparison between normotensive and spontaneously hypertensive rats. Basic Res Cardiol 90, 337–347 (1995). https://doi.org/10.1007/BF00797912

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00797912

Key words

Search

Navigation