Thromb Haemost 1981; 46(04): 676-679
DOI: 10.1055/s-0038-1653450
Original Article
Schattauer GmbH Stuttgart

Effects of Methylprednisolone and Hydrocortisone on Aggregation of Rabbit Platelets Induced by Arachidonic Acid and Other Aggregating Substances

Frank Glass
The Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, U.S.A
,
Howard Lippton
The Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, U.S.A
,
Philip J Kadowitz
The Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, U.S.A
› Author Affiliations
Further Information

Publication History

Received 16 June 1981

Accepted 08 August 1981

Publication Date:
05 July 2018 (online)

Summary

The effects of methylprednisolone and hydrocortisone on platelet aggregation induced by arachidonic acid (AA), collagen, adenosine diphosphate (ADP), prostaglandin (PG) H2, and a stable PGH2 analog, were studied in platelet-rich plasma (PRP) from the rabbit. Incubation of either steroid in PRP inhibited AA-, collagen- and ADP-induced platelet aggregation in a concentration-related manner. The dose of methylprednisolone required to inhibit 0.02 mM AA-induced aggregation was lower than that required to inhibit either 0.08 μg/ml collagen or 0.2 μM ADP-induced aggregation. Methylprednisolone produced a dose dependent inhibition of platelet aggregation induced by PGH2 and the stable PGH2 analog. In washed platelets methylprednisolone was more effective in inhibiting AA-induced aggregation than ADP- or collagen-induced aggregation; however, the difference in effect was less than in PRP. Platelet responses to AA in PRP from rabbits treated with hydrocortisone or methylprednisolone, 100 mg/kg i.v., were inhibited in a transient manner, whereas aggregation induced by ADP under similar conditions was unchanged. Since inhibition of aggregation elicited by AA occurred at concentrations which do not influence PGH2-, PGH2 analog-, collagen- or ADP-induced aggregation, the present data suggest that the steroids may inhibit the incorporation, the release, or the metabolism of arachidonic acid in platelets. The actual mechanism of this relatively specific inhibition of AA-induced aggregation by anti-inflammatory steroids is uncertain but may be related to the membrane “stabilizing” properties of methylprednisolone and hydrocortisone.

 
  • References

  • 1 Kantrowitz F, Robinson DR, McQuire MB, Levine L. Corticosteroids inhibit prostaglandin production by rheumatic synovia. Nature 1975; 258: 737-739
  • 2 Chandrabose KA, Lapetina DG, Schmitges CJ, Siegel MI, Cuatrecasas P. Action of corticosteroids in regulation of prostaglandin biosynthesis in fibroblasts. Proc Natl Acad Sci USA 1978; 75: 214-217
  • 3 Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action of aspirin-like drugs. Nature New Biol 1971; 231: 232-235
  • 4 Dray F, McCall E, Youlten LJ F. Failure of anti-inflammatory steroids to inhibit prostaglandin production by rat polymorphonuclear leucocytes. Br J Pharmacol 1980; 68: 199-205
  • 5 Carnuccio R, DiRosa M, Persico P. Hydrocortisone-induced inhibitor of prostaglandin biosynthesis in rat leucocytes. Br J Pharmacol 1980; 68: 14-16
  • 6 Flower RJ, Blackwell GJ. The importance of phospholipase A2 in prostaglandin biosynthesis. Biochem Pharmacol 1976; 25: 285-291
  • 7 Gryglewski RJ, Panczenko B, Korbut R, Grodzinska L, Ocetkiewicz A. Corticosteroids inhibit prostaglandin release from perfused mesenteric blood vessels of rabbit and from perfused lungs of sensitized guinea pig. Prostaglandins 1975; 10: 343-355
  • 8 Lewis GP, Piper PJ. Inhibition of release of prostaglandins as an explanation of some of the actions of anti-inflammatory corticosteroids. Nature 1975; 254: 308-311
  • 9 Blajchman MA, Hirsh AF, Surya A, Buchanan M. Shortening of bleeding time in rabbits by hydrocortisone caused by inhibition of prostacyclin generation by the vessel wall. J Clin Invest 1979; 63: 1026-1035
  • 10 Russo-Marie F, Paing M, Duval D. Mechanism of glucocorticoid induced inhibition of prostaglandin synthesis. Agents Actions 1979; 4: 49-62
  • 11 Jorgensen KA, Stoffersen E. Hydrocortisone, platelet aggregation and platelet prostaglandin metabolism. Scand J Haematol 1980; 25: 455-457
  • 12 Nelson WR, Taylor GA. In vitro inhibition of endotoxin-induced platelet aggregation with hydrocortisone sodium succinate (Solu-Cortef). Scand J Haematol 1975; 15: 33-44
  • 13 Pierce CH, Oshiro G, Nickerson M. Effects of methylprednisolone sodium succinate (MP) on platelet aggregation. Circulation 1974; 49 (01) 289 (abstract)
  • 14 Cazenave JP, Davies JA, Senyi AF, Blajchman MA, Hirsh J, Mustard JF. Effects of methylprednisolone on platelet adhesion to aorta, bleeding time, and platelet survival. Blood 1976; 48: 1009 (abstract)
  • 15 Rosenberg A, Sanders WJ, Hawiger J. Influence of methylprednisolone on human platelet function: inhibition of aggregation, serotonin release and clot promoting phospholipid irrespective of membrane receptors involved. Clin. Res 1976; 24: 318A (abstract)
  • 16 Ardlie NG, Perry PW, Packham MA, Mustard JF. Influence of apyrase on stability of washed rabbit platelets. Proc Soc Exp Biol Med 1970; 136: 1021-1023
  • 17 She HS, McNamara DB, Spannhake EW, Hyman AL, Kadowitz PJ. Metabolism of prostaglandin endoperoxide by microsomes from cat lung. Prostaglandins 1981; 21: 531-541
  • 18 Born GV. Aggregation of blood platelets by ADP and its reversal. J Physiol (Lond) 1962; 194: 927-929
  • 19 Patrono C, Ciabattoni G, Gvaco F, Grossi-Belloni D. Comparative evaluation of the inhibitory effects of aspirin-like drugs on prostaglandin production by human platelets and synovial tissues. Prostaglandin Thrombox Res 1976; 1: 125-131
  • 20 Hong SL, Levine L. Inhibition of arachidonic acid release from cells as the biochemical action of anti-inflammatory corticosteroids. Proc Natl Acad Sci USA 1976; 73 (05) 1730-1734
  • 21 Glass FL, Lippton HL, Kadowitz PJ. Differential effects of local anesthetics and propranolol on arachidonic acid and adenosine 5’- diphosphate-induced aggregation in rabbit platelets. Prostaglandins and Medicine 1980; 5: 85-92
  • 22 Herbaczynska-Cedro K, Barczak JS. Suppression of the release of prostaglandin-like substances by hydrocortisone in vivo. Prostaglandins 1977; 13 (03) 517-531
  • 23 Chang J, Lewis GP, Piper PJ. Inhibition by glucocorticoids of prostaglandin release from adipose tissue in vitro. Br J Pharmacol 1977; 59: 425-432
  • 24 Bangham AD, Standish MM, Weissmann G. The action of steroids and streptolysin S on the permeability of phospholipid structures to cations. J Mol Biol 1965; 13: 253-259
  • 25 Lewis DA, Symons AM, Ancill RJ. The stabilization-lysis action of anti-inflammatory steroids on lysosomes. J Pharm Pharmacol 1970; 22: 902-908