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Losartanın Yeni Tanı Hipertansiyon Hastalarının Hematolojik Parametrelerine ve Trombosit Agregasyonuna Etkisi

Year 2015, Volume: 16 Issue: 3, 91 - 96, 01.12.2015

Abstract

Amaç: Hipertansiyon artmış trombosit fonksiyonu ile ilişkilidir. Bazı antihipertansif ilaçların anti-trombosit aktiviteleri vardır. Biz bu çalışmada, losartanın adenozin difosfat (ADP), kollajen, epinefrin, ristosetin ile trombosit agregasyonuna, diğer hematolojik ve enflamatuvar parametreler üzerine etkilerinin araştırılmasını amaçladık Gereç ve Yöntem: Çalışmaya yeni tanı hipertansiyonlu ortalama yaşı 54±8 yıl olan 19’u kadın, 6’sı erkek 25 hasta alındı. Yüksek
kan basıncını önleme, saptama, değerlendirme ve tedavi üzerine Birleşik Komite’nin yedinci raporuna göre tüm hastaların, evre 1-2
esansiyel hipertansiyon tanısı mevcuttu. Başlangıç kan basınçları ölçüldü ve her bir hastaya diyet, egzersiz gibi yaşam tarzı değişikliği
ile birlikte losartan 100 mg/gün tedavisi başlandı. Tedavi öncesi ristosetin, epinefrin, kollagen ve ADP ile trombosit agregasyonu
değerlendirildi. Ayrıca tam kan sayımları ölçüldü. Trombosit agregasyon testleri ve kan basıncı ölçümleri tedaviden 8 hafta sonra
tekrar değerlendirildi.
Bulgular: Losartan ile 8 haftanın sonunda sistolik ve diyastolik kan basıncında anlamlı düşüş saptandı (p<0,001). Tedavi sonrası, ADP,
kollajen ve epinefrin seviyeleri ile trombosit agregasyonunda anlamlı farklılık saptanmadı (p>0,05). Ristosetin ile agregasyon önemli
ölçüde azaldı (p=0,027). Aynı zamanda, önemli ölçüde düşük hemoglobin ve hematokrit seviyeleri gözlemlendi (p=0,034 ve 0,039,
sırasıyla).
Sonuç: Losartan, hemoglobin ile hematokrit seviyelerinde ve ristosetinle trombosit agregasyonunda önemli ölçüde düşüş sağlayarak
antihipertansif etkisinden bağımsız aktiviteler ortaya koyabilir. Bu sayede aterosklerozun ve trombozun önlenmesinde faydalı olabilir.

References

  • 1. Wolf M, Heuten HG, De Swaef A, de Falleur M, Verpooten GA. The evolution of hypertension treatment in Belgium, a pharmacoepidemiological study. Acta Cardiol 2012; 67: 147-52.
  • 2. Sato Y, Fujii S, Imagawa S, Ohmura K, Ohmura Y, Andoh Y, et al. Platelet aggregability in patients with hypertension treated with angiotensin II type 1 receptor blockers. J Atheroscler Thromb 2007; 14: 31-5.
  • 3. Chrysant SG, Chrysant GS. The pleiotropic effects of angiotensin receptor blockers. J Clin Hypertens (Greenwich) 2006; 8: 261-8.
  • 4. Andrioli G, Ortolani R, Fontana L, Gaino S, Bellavite P, Lechi C, et al. Study of platelet adhesion in patients with uncomplicated hypertension. J Hypertens 1996; 14: 1215–21.
  • 5. Pathansali R, Smith NM, Bath PM. Prothrombotic megakaryocyte and platelet changes in hypertension are reversed following treatment: a pilot study. Platelets 2001; 12: 144-9.
  • 6. Bavry AA, Li D, Zander DS, Phillips MI, Mehta JL. Inhibition of arterial thrombogenesis by quinapril but not losartan. J Cardiovasc Pharmacol Ther 2000; 5: 121-7.
  • 7. Levy PJ, Yunis C, Owen J, Brosnihan KB, Smith R, Ferrario CM. Inhibition of platelet aggregability by losartan in essential hypertension. Am J Cardiol 2000; 86: 1188-1192.
  • 8. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al; Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003; 42: 1206-52.
  • 9. Ozaki Y, Satoh K, Yatomi Y, Yamamoto T, Shirasawa Y, Kume S. Detection of platelet aggregates with a particle counting method using light scattering. Anal Biochem 1994; 218: 284-94.
  • 10. Tohgi H, Takahashi H, Watanabe K, Kuki H, Shirasawa Y. Development of large platelet aggregates from small aggregates as determined by laser-light scattering: effects of aggregant concentration and antiplatelet medication. Thromb Haemost 1996; 75: 838-43.
  • 11. Gimbrone MA Jr, Topper JN, Nagel T, Anderson KR, GarciaCardena G. Endothelial dysfunction, hemodynamic forces, and atherogenesis. Ann N Y Acad Sci 2000; 902: 230-9.
  • 12. Özsavci D, Şener A, Oba R, Demirel GY, Uras F, Yardımcı TK. New in vitro effects of clopidogrel on platelets in hyperlipidemic and healthy subjects. Turk J Hematol 2010; 27: 99-108.
  • 13. Monton M, Jimenez A, Nunez A, Lopez-Bloya A, Farre J, Gomez J, et al. Comparative effects of angiotensin II AT-1-type receptor antagonists in vitro on human platelet activation. J Cardiovasc Pharmacol 2000; 35: 906-13.
  • 14. Lopez-Farre A, Sanchez de Miguel L, Monton M, Jimenez A, Lopez-Bloya A, Gomez J, et al. Angiotensin II AT(1) receptor antagonists and platelet activation. Nephrol Dial Transplant 2001; 16 Suppl 1: 45-9.
  • 15. Jimenez AM, Monton M, Garcia R, Nuriez A, Gomez J, Rico L, García-Colis E, et al. Inhibition of platelet activation in strokeprone spontaneously hypertensive rats: comparison of losartan, candesartan, and valsartan. J Cardiovasc Pharmacol 2001; 37: 406-12.
  • 16. Yamamoto K, Ozaki H, Takayasu K, Akehi N, Fukui S, Sakai A, et al. The effect of losartan and amlodipine on left ventricular diastolic function and atherosclerosis in Japanese patients with mild-to-moderate hypertension (J-ELAN) study. Hypertens Res 2011;34: 325-30.
  • 17. Chabielska E, Pawlak R, Buczko W. Losartan does not influence the blood platelet aggregation in normotensive rats. Acta Physiol Hung 1996; 84: 271-2.
  • 18. Nossaman BD, Baber SR, Nazim MM, Detrolio JD, Kadowitz PJ. Differential effects of losartan and candesartan on vasoconstrictor responses in the rat. Can J Physiol Pharmacol 2007; 85: 360-71.
  • 19. Nomura S, Shouzu A, Omoto S, Hishikawa M, Fukuhara S, Iwasaka T. Losartan and simvastatin inhibit platelet activation in hypertensive patients. J Thromb Thrombolysis 2004; 18: 177-85.
  • 20. Akdemir R, Ozhan H, Yazici M, Gunudz H, Duran S, Gurel C, et al. In vivo effect of losartan on platelet aggregation in patients with hypertension. Heart Vessels 2004; 19: 167-71.
  • 21. Yamada K, Hirayama T, Hasegawa Y. Antiplatelet effect of losartan and telmisartan in patients with ischemic stroke. J Stroke Cerebrovasc Dis 2007; 16: 225-31.
  • 22. Devereux RB, Dahlöf B. Potential mechanisms of stroke benefit favoring losartan in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Curr Med Res Opin 2007; 23: 443-57.
  • 23. Schwemmer M, Sommer O, Bassenge E. Angiotensin receptor blocker losartan suppresses platelet activity by interfering with thromboxane signaling. Cardiovasc Drugs Ther 2001; 15: 301-7.
  • 24. Jagroop IA, Mikhailidis DP. Angiotensin II can induce and potentiate shape change in human platelets: effect of losartan. J Hum Hypertens 2000; 14: 581-5.
  • 25. Guerra-Cuesta JI, Monton M, Rodriguez-Feo JA, Jimenez AM, Gonzalez-Fernandez F, Rico LA, et al. Effect of losartan on human platelet activation. J Hypertens 1999; 17: 447-52.
  • 26. Ono K, Ueda H, Yoshizawa Y, Akazawa D, Tanimura R, Shimada I, et al. Structural Basis for Platelet Antiaggregation by Angiotensin II Type 1 Receptor Antagonist Losartan (DuP-753) via Glycoprotein VI. J Med Chem 2010; 53: 2087-93.
  • 27. Grothusen C, Umbreen S, Konrad I, Stellos K, Schulz C, Schmidt B, et al. EXP3179 inhibits collagen-dependent platelet activation via glycoprotein receptor-VI independent of AT1-receptor antagonism: potential impact on atherothrombosis. Arterioscler Thromb Vasc Biol 2007; 27: 1184-90.
  • 28. Nunez A, Gomez J, Zalba LR, Monton M, Jimenez A, Velasco S, et al. Losartan inhibits in vitro platelet activation: comparison with candesartan and valsartan. J Renin Angiotensin Aldosterone Syst 2000; 1: 175-9.
  • 29. Prasad K. C-reactive protein (CRP)-lowering agents. Cardiovasc Drug Rev 2006; 24: 33-50.
  • 30. Marathias KP, Agroyannis B, Mavromoustakos T, Matsoukas J, Vlahakos DV. Hematocrit-lowering effect following inactivation of renin-angiotensin system with angiotensin converting enzyme inhibitors and angiotensin receptor blockers. Curr Top Med Chem 2004; 4: 483-6.
  • 31. Sica DA, Mannino R. Antihypertensive medications and anemia. J Clin Hypertens (Greenwich) 2007; 9: 723-7.
  • 32. Breddin HK. Can platelet aggregometry be standardized? Platelets 2005; 16: 151-8.
  • 33. Ghosh K, Nair S, Kulkarni B, Khare A, Shetty S, Mohanty D. Platelet function tests using platelet aggregometry: need for repetition of the test for diagnosis of defective platelet function. Platelets 2003; 14: 351-4.

The Effect of Losartan on Platelet Aggregation and Hematological Parameters in Patients with Newly Diagnosed Hypertension

Year 2015, Volume: 16 Issue: 3, 91 - 96, 01.12.2015

Abstract

Objective: Hypertension is associated with increased platelet function. Some antihypertensive drugs have antiplatelet activity. In this study, we aimed to investigate the effects of losartan on platelet aggregation induced by adenosine diphosphate (ADP), collagen, epinephrine, ristocetin, other hematological and, inflammatory parameters. Materials and Methods: Twenty-five patients (19 female, 6 male; mean age: 54±8 years) with newly diagnosed hypertension were included in the study. All patients were with stage 1-2 essential hypertension according to the seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Initial blood pressure measurement was performed in all patients and losartan 100 mg/daily together with life style changes, such as diet and exercise was started. Platelet aggregation was evaluated with the use of ristocetin, epinephrine, collagen, and ADP. Complete blood count was also done. Platelet aggregation tests and blood pressure measurements were repeated after 8 weeks of therapy. Results: Systolic and diastolic blood pressure significantly decreased with losartan after 8 weeks (p<0.001). After treatment, there was no significant difference in platelet aggregation with ADP, collagen, and epinephrine (p>0.05). The aggregation with ristocetin significantly decreased (p=0.027). Besides, significantly lower hemoglobin and hematocrit levels were observed (p=0.034, p=0.039, respectively). Conclusion: Losartan may produce independent activities apart from its antihypertensive effects by providing significant reductions in platelet aggregation with ristocetin, and in hematocrit levels with hemoglobin. Therefore, it may be beneficial in the prevention of atherosclerosis and thrombosis.

References

  • 1. Wolf M, Heuten HG, De Swaef A, de Falleur M, Verpooten GA. The evolution of hypertension treatment in Belgium, a pharmacoepidemiological study. Acta Cardiol 2012; 67: 147-52.
  • 2. Sato Y, Fujii S, Imagawa S, Ohmura K, Ohmura Y, Andoh Y, et al. Platelet aggregability in patients with hypertension treated with angiotensin II type 1 receptor blockers. J Atheroscler Thromb 2007; 14: 31-5.
  • 3. Chrysant SG, Chrysant GS. The pleiotropic effects of angiotensin receptor blockers. J Clin Hypertens (Greenwich) 2006; 8: 261-8.
  • 4. Andrioli G, Ortolani R, Fontana L, Gaino S, Bellavite P, Lechi C, et al. Study of platelet adhesion in patients with uncomplicated hypertension. J Hypertens 1996; 14: 1215–21.
  • 5. Pathansali R, Smith NM, Bath PM. Prothrombotic megakaryocyte and platelet changes in hypertension are reversed following treatment: a pilot study. Platelets 2001; 12: 144-9.
  • 6. Bavry AA, Li D, Zander DS, Phillips MI, Mehta JL. Inhibition of arterial thrombogenesis by quinapril but not losartan. J Cardiovasc Pharmacol Ther 2000; 5: 121-7.
  • 7. Levy PJ, Yunis C, Owen J, Brosnihan KB, Smith R, Ferrario CM. Inhibition of platelet aggregability by losartan in essential hypertension. Am J Cardiol 2000; 86: 1188-1192.
  • 8. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al; Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003; 42: 1206-52.
  • 9. Ozaki Y, Satoh K, Yatomi Y, Yamamoto T, Shirasawa Y, Kume S. Detection of platelet aggregates with a particle counting method using light scattering. Anal Biochem 1994; 218: 284-94.
  • 10. Tohgi H, Takahashi H, Watanabe K, Kuki H, Shirasawa Y. Development of large platelet aggregates from small aggregates as determined by laser-light scattering: effects of aggregant concentration and antiplatelet medication. Thromb Haemost 1996; 75: 838-43.
  • 11. Gimbrone MA Jr, Topper JN, Nagel T, Anderson KR, GarciaCardena G. Endothelial dysfunction, hemodynamic forces, and atherogenesis. Ann N Y Acad Sci 2000; 902: 230-9.
  • 12. Özsavci D, Şener A, Oba R, Demirel GY, Uras F, Yardımcı TK. New in vitro effects of clopidogrel on platelets in hyperlipidemic and healthy subjects. Turk J Hematol 2010; 27: 99-108.
  • 13. Monton M, Jimenez A, Nunez A, Lopez-Bloya A, Farre J, Gomez J, et al. Comparative effects of angiotensin II AT-1-type receptor antagonists in vitro on human platelet activation. J Cardiovasc Pharmacol 2000; 35: 906-13.
  • 14. Lopez-Farre A, Sanchez de Miguel L, Monton M, Jimenez A, Lopez-Bloya A, Gomez J, et al. Angiotensin II AT(1) receptor antagonists and platelet activation. Nephrol Dial Transplant 2001; 16 Suppl 1: 45-9.
  • 15. Jimenez AM, Monton M, Garcia R, Nuriez A, Gomez J, Rico L, García-Colis E, et al. Inhibition of platelet activation in strokeprone spontaneously hypertensive rats: comparison of losartan, candesartan, and valsartan. J Cardiovasc Pharmacol 2001; 37: 406-12.
  • 16. Yamamoto K, Ozaki H, Takayasu K, Akehi N, Fukui S, Sakai A, et al. The effect of losartan and amlodipine on left ventricular diastolic function and atherosclerosis in Japanese patients with mild-to-moderate hypertension (J-ELAN) study. Hypertens Res 2011;34: 325-30.
  • 17. Chabielska E, Pawlak R, Buczko W. Losartan does not influence the blood platelet aggregation in normotensive rats. Acta Physiol Hung 1996; 84: 271-2.
  • 18. Nossaman BD, Baber SR, Nazim MM, Detrolio JD, Kadowitz PJ. Differential effects of losartan and candesartan on vasoconstrictor responses in the rat. Can J Physiol Pharmacol 2007; 85: 360-71.
  • 19. Nomura S, Shouzu A, Omoto S, Hishikawa M, Fukuhara S, Iwasaka T. Losartan and simvastatin inhibit platelet activation in hypertensive patients. J Thromb Thrombolysis 2004; 18: 177-85.
  • 20. Akdemir R, Ozhan H, Yazici M, Gunudz H, Duran S, Gurel C, et al. In vivo effect of losartan on platelet aggregation in patients with hypertension. Heart Vessels 2004; 19: 167-71.
  • 21. Yamada K, Hirayama T, Hasegawa Y. Antiplatelet effect of losartan and telmisartan in patients with ischemic stroke. J Stroke Cerebrovasc Dis 2007; 16: 225-31.
  • 22. Devereux RB, Dahlöf B. Potential mechanisms of stroke benefit favoring losartan in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Curr Med Res Opin 2007; 23: 443-57.
  • 23. Schwemmer M, Sommer O, Bassenge E. Angiotensin receptor blocker losartan suppresses platelet activity by interfering with thromboxane signaling. Cardiovasc Drugs Ther 2001; 15: 301-7.
  • 24. Jagroop IA, Mikhailidis DP. Angiotensin II can induce and potentiate shape change in human platelets: effect of losartan. J Hum Hypertens 2000; 14: 581-5.
  • 25. Guerra-Cuesta JI, Monton M, Rodriguez-Feo JA, Jimenez AM, Gonzalez-Fernandez F, Rico LA, et al. Effect of losartan on human platelet activation. J Hypertens 1999; 17: 447-52.
  • 26. Ono K, Ueda H, Yoshizawa Y, Akazawa D, Tanimura R, Shimada I, et al. Structural Basis for Platelet Antiaggregation by Angiotensin II Type 1 Receptor Antagonist Losartan (DuP-753) via Glycoprotein VI. J Med Chem 2010; 53: 2087-93.
  • 27. Grothusen C, Umbreen S, Konrad I, Stellos K, Schulz C, Schmidt B, et al. EXP3179 inhibits collagen-dependent platelet activation via glycoprotein receptor-VI independent of AT1-receptor antagonism: potential impact on atherothrombosis. Arterioscler Thromb Vasc Biol 2007; 27: 1184-90.
  • 28. Nunez A, Gomez J, Zalba LR, Monton M, Jimenez A, Velasco S, et al. Losartan inhibits in vitro platelet activation: comparison with candesartan and valsartan. J Renin Angiotensin Aldosterone Syst 2000; 1: 175-9.
  • 29. Prasad K. C-reactive protein (CRP)-lowering agents. Cardiovasc Drug Rev 2006; 24: 33-50.
  • 30. Marathias KP, Agroyannis B, Mavromoustakos T, Matsoukas J, Vlahakos DV. Hematocrit-lowering effect following inactivation of renin-angiotensin system with angiotensin converting enzyme inhibitors and angiotensin receptor blockers. Curr Top Med Chem 2004; 4: 483-6.
  • 31. Sica DA, Mannino R. Antihypertensive medications and anemia. J Clin Hypertens (Greenwich) 2007; 9: 723-7.
  • 32. Breddin HK. Can platelet aggregometry be standardized? Platelets 2005; 16: 151-8.
  • 33. Ghosh K, Nair S, Kulkarni B, Khare A, Shetty S, Mohanty D. Platelet function tests using platelet aggregometry: need for repetition of the test for diagnosis of defective platelet function. Platelets 2003; 14: 351-4.
There are 33 citations in total.

Details

Other ID JA98JA47RA
Journal Section Research Article
Authors

Mustafa Ünübol This is me

İrfan Yavaşoğlu This is me

Bilal Acar This is me

Gürhan Kadıköylü This is me

Zahit Bolaman This is me

Publication Date December 1, 2015
Published in Issue Year 2015 Volume: 16 Issue: 3

Cite

EndNote Ünübol M, Yavaşoğlu İ, Acar B, Kadıköylü G, Bolaman Z (December 1, 2015) The Effect of Losartan on Platelet Aggregation and Hematological Parameters in Patients with Newly Diagnosed Hypertension. Meandros Medical And Dental Journal 16 3 91–96.