Skip to main content
Log in

Inotropic actions of eicosanoids

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

Summary

Eicosanoids (prostaglandins, leukotrienes, thromboxane A2 and other metabolites of C-20 polyunsaturated fatty acids) have numerous effects in the cardiovascular system. Direct inotropic actions have been repeatedly described, but appear in only very few cases to be due to direct modification of the inotropic state of the heart. Specific eicosanoid receptors have been identified on the surface of the sarcolemmal membrane. Signal transduction pathways in the cardiac myocyte involve the adenylate cyclase/cAMP system or stimulation of the phospholipase C/IP3 pathway. In general, concentrations of eicosanoids which affect myocardial contractility are higher as the response is less predictable than the effects on platelet function or vessel tone. Therefore, eicosanoid-induced extracardiac effects may be superimposed to more direct changes in the contractile state of the intact heart in vitro or in vivo. In contrast to non-failing hearts, there is a significant improvement of the contractile function in contractile failure (“stunning”, ischemia, congestive heart failure) by vasodilating prostaglandins (e.g., PGI2). The mechanism of this action is still unknown.

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

Access this article

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

Instant access to the full article PDF.

References

  1. Allan G, Levi R (1980) The cardiac effects of prostaglandins and their modification by the prostaglandin antagonist N-0164. J Pharm Exp Ther 214:45–49

    Google Scholar 

  2. Alloatti G, Serazzi L, Levi RC (1991) Prostaglandin I2 (PGI2) enhances calcium current in guinea-pig ventricular heart cells. J Mol Cell Cardiol 23:851–860

    Google Scholar 

  3. Auclair MC, Vernimmen C, Lechat P (1988) Influence of prostacyclin and two metabolites om the contractility of cultured rat heart cells. Prostaglandins Leukotr Essent Fatty Acids 32:33–38

    Google Scholar 

  4. Auinger C, Weissel M, Bergmann H, Sinzinger H (1988) Einfluß von PGE1 auf die linksventrikuläre Auswurffraktion. Wien Klin Wochenschr 100:706–709

    Google Scholar 

  5. Awan NA, Evenson MK, Needham KE, Beattie JM, Amsterdam ED, Mason DT (1981) Cardiocirculatory and myocardial energetic effects of prostaglandin E1 in severe left ventricular failure due to chronic coronary heart disease. Am Heart J 102:703–709

    Google Scholar 

  6. Bjoernsson OG, Kobayashi K, Williamson JR (1987) Interaction between leukotriene D4 and adenosine or iloprost in the isolated working guinea-pig heart: prevention of the leukotriene D4 effect. Eur J Clin Invest 17:146–155

    Google Scholar 

  7. Borda LS, Cangas L, Gimeno MF, Gimeno AL (1979) An adrenergic participation subserving a positive inotropism and chronotropism of prostacyclin on isolated rat atria. Experientia 35:529–530

    Google Scholar 

  8. Burke JA, Levi R, Guo ZG, Corey EJ (1982) Leukotrienes C4, D4 and E4: effects on human and guinea-pig cardiac preparations in vitro. J Pharmacol Exp Ther 221:235–241

    Google Scholar 

  9. Cannon PJ (1986) Prostaglandins in congestive heart failure and the effects of nonsteroidal antiinflammatory drugs. Am J Med 81:123–132

    Google Scholar 

  10. Couttenye MM, De Clerck NM, Herman AG, Brutsaert DL (1985) Effects of prostacyclin on contractile properties of isolated mammalian cardiac muscle. J Cardiovasc Pharmacol 7:971–976

    Google Scholar 

  11. Das UN, Lee AM, Barritt GJ (1983) Prostanoids can modify response to electrical stimulus and45Ca2+ exchange in isolated myocardial muscle cells. Prostaglandins Leukotr Med 12:305–314

    Google Scholar 

  12. Dzau VJ, Packer M, Lilly LS, Swartz SL, Hollenberg NK, Williams GH (1984) Prostaglandins in severe congestive heart failure. Relation to activation of the renin-angiotensin system and hyponatremia. New Engl J Med 310:347–352

    Google Scholar 

  13. Falcone RC, Aharony D, Orzechowski F (1991) Evidence for leukotriene D4 receptors in guinea pig left atria. J Pharmacol Exp Ther 258:199–206

    Google Scholar 

  14. Farber NE, Gross GJ (1989) Prostaglandin E1 attenuates postischemic contractile dysfunction after brief coronary occlusion and reperfusion. Am Heart J 118:17–24

    Google Scholar 

  15. Farber NE, Gross GJ (1990) Prostaglandin redirection by thromboxane synthetase inhibition. Circulation 81:369–380

    Google Scholar 

  16. Farber NE, Pieper GM, Thomas JP, Gross GJ (1988) Beneficial effects of iloprost in the stunned canine myocardium. Circ Res 62:204–215

    Google Scholar 

  17. Fassina G, Tessari F, Dorigo P (1983) Positive inotropic effect of a stable analogue of PGI2 and of isolated guinea pig atria. Mechanism of action. Pharmacol Res Commun 15:735–749

    Google Scholar 

  18. Garlick PB, Mashiter GD, Di Marzo V, Tippins JR, Morris HR, Maisey MN (1989) The synthesis, release and action of leukotrienes in the isolated, unstimulated, buffer-perfused rat heart. J Mol Cell Cardiol 21:1101–1110

    Google Scholar 

  19. Hattori Y, Levi R (1984) Negative inotropic effect of leukotrienes: leukotrienes C4 and D4 inhibit calcium-dependent contractile responses in potassium-depolarized guinea-pig myocardium. J Pharmacol Exp Ther 230:646–651

    Google Scholar 

  20. Hattori Y, Levi R (1986) Effect of PGD2 on cardiac contractility: a negative inotropism secondary to coronary vasoconstriction conceals a primary positive inotropic action. J Pharm Exp Ther 237:719–724

    Google Scholar 

  21. Hayes JB, Bowling N, King KL, Boder GB (1982) Evidence for selective regulation of the phosphorylation of myocyte proteins by isoproterenol and prostaglandin E1. Biochim Biophys Acta 714:136–142

    Google Scholar 

  22. Härtel B, Morwinski R, Heydeck D, Papies B (1991) Arachidonic acid metabolism in cultured adult myocardial cells under short-time hypoxic conditions. Mol Cell Biochem 106:67–74

    Google Scholar 

  23. Hedqvist P, Wennmalm A (1971) Comparison of the effects of prostaglandins E1, E2 and F on the sympathetically stimulated rabbit heart. Acta Physiol Scand 83:156–162

    Google Scholar 

  24. Herman RP, Heller RS, Canavan CM, Herman CA (1988) Leukotriene C4 action and metabolism in the isolated perfused bullfrog heart. Can J Physiol Pharmacol 66:980–984

    Google Scholar 

  25. Hogaboom GK, Mong S, Stadel JM, Crooke ST (1985) Characterization of guinea pig myocardial leukotriene C4 binding sites. Regulation by cations and sulfhydryl-directed agents. Mol Pharmacol 27:236–245

    Google Scholar 

  26. Hohl CM, Rösen P (1987) The role of arachidonic acid in rat heart cell metabolism. Biochim Biophys Acta 921:356–360

    Google Scholar 

  27. Hohlfeld Th, Strobach H, Schrör K (1991) Stimulation of prostacyclin synthesis by defibrotide: improved contractile recovery from myocardial ‘stunning’. J Cardiovasc Pharmacol 17:108–115

    Google Scholar 

  28. Holzgrefe HH, Buchanan LV, Bunting S (1987) In vivo characterization of synthetic thromboxane A2 in canine myocardium. Circ Res. 60:290–966

    Google Scholar 

  29. Huang JM, Xian Hu, Bacaner M (1991) Leukotrienes and prostaglandins signal biologic actions by modulating calcium current in guinea pig myocytes. Circulation 84: (Suppl II) II-209

    Google Scholar 

  30. Huang JM, Xian Hu, Bacaner M (1990) Arachidonic acid and metabolites modulate calcium currents in single ventricular myocytes. Circulation 83: (Suppl III) III-525

    Google Scholar 

  31. Kangasaho M, Metsae-Ketelae T, Vapaatalo H (1978) Effects of prostaglandins on rat cardiac adenylate cyclase. Eur J Pharmacol 52:93–98

    Google Scholar 

  32. Karmazyn M, Dhalla NS (1979) Thromboxane B2: a cardiodepressant of isolated rat hearts and inhibitor of sarcolemma Na+ and K+ stimulated ATPase activity. Prostaglandins Med 3:81–93

    Google Scholar 

  33. Karmazyn M, Moffat MP (1990) Positive inotropic effects of low concentrations of leukotrienes C4 and D4 in rat heart. Am J Physiol 259:H1239-H1246

    Google Scholar 

  34. Kaumann AJ, Birnbaumer L (1974) Prostaglandin E1 action on sinus pacemaker and adenylyl cyclase in kitten myocardium. Nature 251:515–517

    Google Scholar 

  35. Keely SL (1979) Prostaglandin E1 activation of heart cAMP-dependent protein kinase: apparent dissociation of protein kinase activation from increases in phosphorylase activity and contractile force. Mol Pharmacol 15:235–245

    Google Scholar 

  36. Krebs R, Schrör K (1975) Actions of prostaglandin E2 on myocardial mechanisms, coronary vascular resistance and oxygen consumption in the guinea-pig isolated heart preparation. Br J Pharmacol 55:403–408

    Google Scholar 

  37. Krzeminski T, Kurcok A, Juraszczyk Z, Kozik W, Kapustecki J, Kryj M, Brus R (1987) Influence of verapamil on central and peripheral effects of prostacyclin on circulatory system in rats. Med Biol 65:249–253

    Google Scholar 

  38. Letts LG, Piper PJ (1982) The actions of leukotrienes C4 and D4 on guinea-pig isolated hearts. Br J Pharmacol 76:169–176

    Google Scholar 

  39. Lopaschuk GD, Michalak M, Wandler EL, Lerner RW, Piscione TD, Coceani F, Olley PM (1989) Prostaglandin E receptors in cardiac sarcolemma. Circ Res 65:538–545

    Google Scholar 

  40. Metsae-Ketelae T (1981) Cyclic AMP dependent and -independent effects of prostaglandins on the contraction-relaxation cycle of spontaneously beating rat atria. Acta Physiol Scand 112:481–485

    Google Scholar 

  41. Mironeau J, Grosset A (1976) Ionic mechanism of inotropic effect of prostaglandin E1 on frog atrial muscle. Pflüger's Arch 366:79–81

    Google Scholar 

  42. Morgan JP (1991) Abnormal intracellular modulation of calcium as a major cause of cardiac contractile dysfunction. New Engl J Med 325:625–632

    Google Scholar 

  43. Mullane KM, Fornabaio D (1988) Thromboxane synthetase inhibitors reduce infarct size by a platelet-dependent, aspirin-sensitive mechanism. Circ Res 62:668–678

    Google Scholar 

  44. Otani H, Otani H, Das DK (1988) Positive inotropic effect and phosphoinositide breakdown mediated by arachidonic acid and prostaglandin F. J Pharm Exp Ther 244:844–851

    Google Scholar 

  45. Ragazzi E, Salvador S, Froldi G (1990) Interaction of FCE 22176, a stable prostacyclin analogue, with different prostaglandins in guinea-pig trachea and atria. Pharmacol Res 22:263–269

    Google Scholar 

  46. Robleto DO, Reitmeyer ST, Herman CA (1988) Cardiac inotropic effects of leukotriene C4 and prostaglandin I2 in the unanesthetized American bullfrog, Rana catesbeiana. Can J Physiol Pharmacol 66:233–238

    Google Scholar 

  47. Roth DM, Reibel DK, Lefer AM (1984) Altered coronary vascular responsiveness to leukotrienes in alloxan-diabetic rats. Circ Res 54:388–395

    Google Scholar 

  48. Sakuma I, Gross SS, Levi R (1989) Positive inotropic effect of the thromboxane analogue U-46619 on guinea pig left atrium: mediation by specific receptors and association with increased phosphoinositide turnover. Can J Physiol Pharmacol 67:943–949

    Google Scholar 

  49. Schrör K (1978) Prostaglandin D2—a potent coronary vasoconstrictor agent in the guinea pig isolated heart. Naunyn-Schmiedeberg's Arch Pharmacol 302:61–62

    Google Scholar 

  50. Schrör K (1987) Actions of prostaglandins on the heart. In: Gryglewski RJ, Stock G (eds) Prostacyclin and its stable analog iloprost; Springer, Berlin Heidelberg, pp 159–178

    Google Scholar 

  51. Schrör K (1988) Cardiac muscle and coronary vessels. In: Curtis-Prior P (ed) Prostaglandins; Churchill-Livingstone, London, pp 238–268

    Google Scholar 

  52. Schrör K, Hohlfeld Th (1990) Eicosanoids and the ischemic myocardium. In: Piper HM (ed) Pathophysiology of severe myocardial injury; Kluwer, Dordrecht, Netherlands, pp 195–220

    Google Scholar 

  53. Schrör K, Link H-B, Rösen R, Klaus W, Rösen P (1980) Prostacyclin-induced coronary vasodilation. Interactions with adenosine, cyclic AMP and energy charge in the rat heart in vitro. Eur J Pharmacol 64:341–348

    Google Scholar 

  54. Schrör K, Moncada S (1979) Effect of prostacyclin on coronary circulation, heart rate and myocardial contractile force in isolated hearts of guinea pig and rabbit — comparison with prostaglandin E2. Prostaglandins 17:367–373

    Google Scholar 

  55. Shaffer JE, Malik KU (1984) Mechanism of action of arachidonic acid in the isolated perfused rat heart. Can J Physiol Pharmacol 62:551–558

    Google Scholar 

  56. Sterin-Borda L, Canga L, Borda ES, Gimeno MF, Gimeno AL (1980) Inotropic effect of prostacyclin (PGI2) on isolated rat atria at different contraction frequencies. Naunyn-Schmiedeberg's Arch Pharmacol 313:95–100

    Google Scholar 

  57. Sterin-Borda L, Canga L, Pissani A, Gimeno AL (1980) Inotropic effect of PGE1 and PGE2 on isolated rat atria. Influence of adrenergic mechanisms. Prostaglandins 20:825–836

    Google Scholar 

  58. Terashita ZI, Fukui H, Nishikawa K, Hirata M, Kikuchi S (1978) Coronary vasospastic action of thromboxane A2 in isolated, working guinea pig hearts. Eur J Pharmacol 53:49–56

    Google Scholar 

  59. Uemura S, Nakanishi T, Matsuoka S (1984) Inotropic effects of prostaglandin D2 and E1 on the newborn rabbit heart. Pediatr Res 18:1277–1281

    Google Scholar 

  60. Wennmalm M, FitzGerald GA, Wennmalm A (1987) Prostacyclin as neuromodulator in the sympathetically stimulated rabbit heart. Prostaglandins 33:675–691

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schrör, K., Hohlfeld, T. Inotropic actions of eicosanoids. Basic Res Cardiol 87, 2–11 (1992). https://doi.org/10.1007/BF00795384

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00795384

Key words

Navigation