Skip to main content
SpringerLink
Log in

Effects of various doses of aspirin on platelet activity and endothelial function

  • Original Article
  • Published:
Heart and Vessels Aims and scope Submit manuscript

Abstract

Although aspirin has become an established medicine for cardiac and cerebrovascular diseases, the optimal dose remains unknown. We evaluated the optimal dose of aspirin on platelet activity and endothelial function by administering 11 healthy male volunteers (32 ± 6 years of age) doses of aspirin that were increased in a stepwise manner (0, 81, 162, 330 and 660 mg/day) every 3 days. Platelet activity was assessed as surface P-selectin expression (%) measured by flow cytometry and the platelet aggregation ratio. Endothelial function in the brachial artery was assessed by measuring flow-mediated dilation (FMD) before and after reactive hyperemia. Platelet aggregation and P-selectin expression were significantly and dose-dependently suppressed (81–660 mg), and the FMD ratio tended to increase from 0 to 162 mg, but decreased significantly at 660 mg. In conclusion, although aspirin suppressed platelet activity and even surface P-selectin expression, higher doses worsened endothelial-mediated arterial dilation.

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

Fig. 1

Similar content being viewed by others

References

  1. Elwood PC, Cochrane AL, Burr ML, Sweetnam PM, Williams G, Welsby E, Hughes SJ, Renton R (1974) A randomized controlled trial of acetyl salicylic acid in the secondary prevention of mortality from myocardial infarction. Br Med J 1:436–440

    Article  PubMed  CAS  Google Scholar 

  2. Steering Committee of the Physicians’ Health Study Research Group (1989) Final report on the aspirin component of the ongoing Physicians’ Health Study. N Engl J Med 321:129–135

    Article  Google Scholar 

  3. Peto R, Gray R, Collins R, Wheatley K, Hennekens C, Jamrozik K, Warlow C, Hafner B, Thompson E, Norton S, Gilliland J, Doll R (1988) Randomised trial of prophylactic daily aspirin in British male doctors. Br Med J (Clin Res Ed) 296(6618):313–316

    Article  CAS  Google Scholar 

  4. Hebert PR, Hennekens CH (2000) An overview of the four randomized trials of aspirin therapy in the primary prevention of vascular disease. Arch Intern Med 160:3123–3127

    Article  PubMed  CAS  Google Scholar 

  5. Kubota N, Kasai T, Miyauchi K, Njaman W, Kajimoto K, Akimoto Y, Kojima T, Ken Y, Takeshi K, Hiroyuki D (2008) Therapy with statins and aspirin enhances long-term outcome of percutaneous coronary intervention. Heart Vessels 23:35–39

    Article  PubMed  Google Scholar 

  6. Antithrombotic Trialists’ Collaboration (2002) Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Br Med J 324:71–86

    Article  Google Scholar 

  7. Dyken ML, Barnett HJ, Easton JD, Fields WS, Fuster V, Hachinski V, Norris JW, Sherman DG (1992) Low-dose aspirin and stroke. “It ain’t necessarily so”. Stroke 23:1395–1399

    PubMed  CAS  Google Scholar 

  8. Barnett HJ, Kaste M, Meldrum H, Eliasziw M (1996) Aspirin dose in stroke prevention: beautiful hypotheses slain by ugly facts. Stroke 27:588–592

    PubMed  CAS  Google Scholar 

  9. Taylor DW, Barnett HJ, Haynes RB, Ferguson GG, Sackett DL, Thorpe KE, Simard D, Silver FL, Hachinski V, Clagett GP, Barnes R, Spence JD (1999) Low-dose and high-dose acetylsalicylic acid for patients undergoing carotid endarterectomy: a randomised controlled trial. ASA and Carotid Endarterectomy (ACE) Trial Collaborators. Lancet 353:2179–2184

    Article  PubMed  CAS  Google Scholar 

  10. Moncada S, Gryglewski R, Bunting S, Vane JR (1976) An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 263:663–665

    Article  PubMed  CAS  Google Scholar 

  11. Willems C, De Groot PG, Pool GA, Gonsalvez MS, Van Aken WG, Van Mourik JA (1982) Arachidonate metabolism in cultured human vascular endothelial cells. Evidence for two prostaglandin synthetic pathways sensitive to acetylsalicylic acid. Biochim Biophys Acta 713:581–588

    PubMed  CAS  Google Scholar 

  12. Ozturk O, Greaves M, Templeton A (2002) Aspirin dilemma. Remodelling the hypothesis from a fertility perspective. Hum Reprod 17:1146–1148

    Article  PubMed  CAS  Google Scholar 

  13. Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, Vallance P, Vita J, Vogel R, International Brachial Artery Reactivity Task Force (2002) Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 39:257–265

    Article  PubMed  Google Scholar 

  14. Witte DR, Westerink J, de Koning EJ, van der Graaf Y, Grobbee DE, Bots ML (2005) Is the association between flow-mediated dilation and cardiovascular risk limited to low-risk populations? J Am Coll Cardiol 45:1987–1993

    Article  PubMed  Google Scholar 

  15. Dogra G, Rich L, Stanton K, Watts GF (2001) Endothelium-dependent and independent vasodilation studies at normoglycaemia in type I diabetes mellitus with and without microalbuminuria. Diabetologia 44:593–601

    Article  PubMed  CAS  Google Scholar 

  16. Yeboah J, Crouse JR, Hsu FC, Burke GL, Herrington DM (2007) Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: the Cardiovascular Health Study. Circulation 115:2390–2397

    Article  PubMed  Google Scholar 

  17. Mizia-Stec K, Gasior Z, Zahorska-Markiewicz B, Holecki M, Haberka M, Mizia M, Gomułka S, Zak-Gołab A, Gościńska A (2008) The indexes of arterial structure and function in women with simple obesity: a preliminary study. Heart Vessels 23:224–229

    Article  PubMed  Google Scholar 

  18. Fujii N, Tsuchihashi K, Sasao H, Eguchi M, Miurakami H, Hase M, Higashiura K, Yuda S, Hashimoto A, Miura T, Ura N, Shimamoto K (2008) Insulin resistance functionally limits endothelium-dependent coronary vasodilation in nondiabetic patients. Heart Vessels 23:9–15

    Article  PubMed  Google Scholar 

  19. Crisby M, Kublickiene K, Henareh L, Agewall S (2009) Circulating levels of autoantibodies to oxidized low-density lipoprotein and C-reactive protein levels correlate with endothelial function in resistance arteries in men with coronary heart disease. Heart Vessels 24:90–95

    Article  PubMed  Google Scholar 

  20. Pohl U, Holtz J, Busse R, Bassenge E (1986) Crucial role of endothelium in the vasodilator response to increased flow in vivo. Hypertension 8:37–44

    PubMed  CAS  Google Scholar 

  21. Joannides R, Haefeli WE, Linder L, Richard V, Bakkali EH, Thuillez C, Lüscher TF (1995) Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. Circulation 91:1314–1319

    PubMed  CAS  Google Scholar 

  22. Husain S, Andrews NP, Mulcahy D, Panza JA, Quyyumi AA (1998) Aspirin improves endothelial dysfunction in atherosclerosis. Circulation 97:716–720

    PubMed  CAS  Google Scholar 

  23. Sun D, Huang A, Smith CJ, Stackpole CJ, Connetta JA, Shesely EG, Koller A, Kaley G (1999) Enhanced release of prostaglandins contributes to flow-induced arteriolar dilation in eNOS knockout mice. Circ Res 85:288–293

    PubMed  CAS  Google Scholar 

  24. Taubert D, Berkels R, Grosser N, Schröder H, Gründemann D, Schömig E (2004) Aspirin induces nitric oxide release from vascular endothelium: a novel mechanism of action. Br J Pharmacol 143:159–165

    Article  PubMed  CAS  Google Scholar 

  25. Born GV (1962) Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 194:927–929

    Article  PubMed  CAS  Google Scholar 

  26. O’brien JR (1962) Platelet aggregation: Part I some effects of the adenosine phosphates, thrombin, and cocaine upon platelet adhesiveness. J Clin Pathol 15:446–452

    Article  PubMed  Google Scholar 

  27. Peters MJ, Heyderman RS, Hatch DJ, Klein NJ (1997) Investigation of platelet-neutrophil interactions in whole blood by flow cytometry. J Immunol Methods 209:125–135

    Article  PubMed  CAS  Google Scholar 

  28. Yamasaki F, Furuno T, Sato K, Zhang D, Nishinaga M, Sato T, Doi Y, Sugiura T (2005) Association between arterial stiffness and platelet activation. J Hum Hypertens 19:527–533

    Article  PubMed  CAS  Google Scholar 

  29. Ridker PM, Cook NR, Lee IM, Gordon D, Gaziano JM, Manson JE, Hennekens CH, Buring JE (2005) A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med 352:1293–1304

    Article  PubMed  CAS  Google Scholar 

  30. Gori T, Dragoni S, Lisi M, Di Stolfo G, Sonnati S, Fineschi M, Parker JD (2008) Conduit artery constriction mediated by low flow a novel noninvasive method for the assessment of vascular function. J Am Coll Cardiol 51:1953–1958

    Article  PubMed  Google Scholar 

  31. Cahill MR, Newland AC (1993) Platelet activation in coronary artery disease. Br J Biomed Sci 50:221–234

    PubMed  CAS  Google Scholar 

  32. Hung J, Lam JY, Lacoste L, Letchacovski G (1995) Cigarette smoking acutely increases platelet thrombus formation in patients with coronary artery disease taking aspirin. Circulation 92:2432–2436

    PubMed  CAS  Google Scholar 

  33. Steinhubl SR, Moliterno DJ (1997) Glycoprotein IIb/IIIa receptor antagonists for the treatment of unstable angina. Heart Vessels Suppl 12:148–155

    Google Scholar 

  34. Sacco M, Pellegrini F, Roncaglioni MC, Avanzini F, Tognoni G, Nicolucci A, PPP Collaborative Group (2003) Primary prevention of cardiovascular events with low-dose aspirin and vitamin E in type 2 diabetic patients: results of the Primary Prevention Project (PPP) trial. Diabetes Care 26:3264–3272

    Article  PubMed  CAS  Google Scholar 

  35. Blann AD, Dobrotova M, Kubisz P, McCollum CN (1995) von Willebrand factor, soluble P-selectin, tissue plasminogen activator and plasminogen activator inhibitor in atherosclerosis. Thromb Haemost 74:626–630

    PubMed  CAS  Google Scholar 

  36. Davì G, Romano M, Mezzetti A, Procopio A, Iacobelli S, Antidormi T, Bucciarelli T, Alessandrini P, Cuccurullo F, Bittolo Bon G (1998) Increased levels of soluble P-selectin in hypercholesterolemic patients. Circulation 97:953–957

    PubMed  Google Scholar 

  37. Cannon CP, McLean DS (2006) Critical pathways using platelet testing to potentially optimize the use of oral antiplatelet therapy. Am J Cardiol 98:33N–38N

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Tadashi Ueta for excellent technical assistance. We also thank Misa Nakagawa, Yanan Zhang and Dongmei Zhang for technical assistance throughout the study.

Author information

Authors and Affiliations

  1. Medicine and Geriatrics, Kochi Medical School, Nankoku, Kochi, 783-8505, Japan

    Takashi Furuno, Kyoko Sato & Yoshinori Doi

  2. Clinical Laboratory, Kochi Medical School, Nankoku, Kochi, 783-8505, Japan

    Fumiyasu Yamasaki & Tetsuro Sugiura

  3. Anesthesiology, Kochi Medical School, Nankoku, Kochi, 783-8505, Japan

    Takeshi Yokoyama

  4. Cardiovascular Control, Kochi Medical School, Nankoku, Kochi, 783-8505, Japan

    Takayuki Sato

Authors
  1. Takashi Furuno
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fumiyasu Yamasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takeshi Yokoyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kyoko Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takayuki Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yoshinori Doi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tetsuro Sugiura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fumiyasu Yamasaki.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Furuno, T., Yamasaki, F., Yokoyama, T. et al. Effects of various doses of aspirin on platelet activity and endothelial function. Heart Vessels 26, 267–273 (2011). https://doi.org/10.1007/s00380-010-0054-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00380-010-0054-8

Keywords

Search

Navigation