Menu

A+ A A-

Download article

Delevskaya V.Y.
The influence of spironolactone on extracellular matrix metabolism in patients with arterial hypertension and concomitant chronic obstructive pulmonary disease
Kharkiv National Medical University, the Ukraine

Abstract.
Objectives. To study the effect of aldosterone receptors blockade on extracellular matrix metabolism in patients with arterial hypertension combined with chronic obstructive pulmonary disease.
Material and methods. A total of 80 patients with arterial hypertension combined with chronic obstructive pulmonary disease of II-III degree of airways obstruction were included in the study. All patients were divided into 2 groups. The first group (41 patients) received basic therapy and the second group (39 patients) additionally received spironolactone in a daily dose of 50 mg during 3 months. Thw level of glycosaminoglycanes in the blood serum of patients was measured by resorcin method and MMP-9 – by enzyme-linked immunosorbent assay. All patients underwent laboratory investigation before and after the treatment.
Results. The obtained results have shown, that the addition of spironolactone to the basic treatment of patients with arterial hypertension and chronic obstructive pulmonary disease led to the decreased level of serum chondroitin-6-sulphates and the increased level of heparansulfates/keratansulfates, which was accompanied by the decrease of MMP-9 level in the blood serum (p<0,05). No adverse effects while using spironolactone were registered in the studied patients.
Conclusions. The addition of spironolactone to the basic treatment of heart failure in the patients with arterial hypertension and chronic obstructive pulmonary disease results in positive changes of ECM metabolism and the reduction in the activity of connective tissue degradation processes, that might contribute to the positive effect of spironolactone on cardiovascular system and progression of heart failure.
Key words: spironolactone, glycosaminoglycanes, matrix metalloprotease-9, chronic obstructive pulmonary disease, arterial hypertension.

References

       1. Rutten FH. Diagnosis and management of heart failure in COPD. Eur Respir Monogr. 2013;(59):50–63.
       2. Rusinaru D, Saaidi I, Godard S, Mahjoub H, Battle C, Tribouilloy C. Impact of chronic obstructive pulmonary disease on long-term outcome of patients hospitalized for heart failure. Am J Cardiol. 2008 Feb 1;101(3):353-8.
       3. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med. 1999 Sep;341(10):709-17.
       4. Annoni R, Lanças T, Yukimatsu Tanigawa R, de Medeiros Matsushita M, de Morais Fernezlian S, Bruno A, Fernando Ferraz da Silva L, Roughley PJ, Battaglia S, Dolhnikoff M, Hiemstra PS, Sterk PJ, Rabe KF, Mauad T. Extracellular matrix composition in COPD. Eur Respir J. 2012 Dec;40(6):1362-73.
       5. Cullmann D, Burgard G, inventors. Use of Hyaluronidase for the Prevention or Treatment of Arterial Hypertension or Cardiac Insufficiency. US patent 2010/0092450 A1 Apr 15.
       6. Brajer B, Batura-Gabryel H, Nowicka A, Kuznar-Kaminska B, Szczepanik A. Concentration of matrix metalloproteinase-9 in serum of patients with chronic obstructive pulmonary disease and a degree of airway obstruction and disease progression. J Physiol Pharmacol. 2008 Dec;59(6):145-52.
       7. Yasmin, McEniery CM, Wallace S, Dakham Z, Pulsalkar P, Maki-Petaja K, Ashby MJ, Cockcroft JR, Wilkinson IB. Matrix Metalloproteinase-9 (MMP-9), MMP-2, and Serum Elastase Activity are Associated with Systolic Hypertension and Arterial Stiffness. Arterioscler Thromb Vasc Biol. 2005 Feb;25(2):372.
       8. Funayama H, Ishikawa SE, Kubo N, Katayama T, Yasu T, Saito M, Kawakami M. Increases in Interleukin-6 and Matrix Metalloproteinase-9 in the Infarct-Related Coronary Artery of Acute Myocardial Infarction. Circ J. 2004 May;68(5):451-4.
       9. Tayebjee MH, Nadar SK, MacFadyen RJ, Lip GY. Tissue inhibitor of MMP-1 and MMP-9 levels in patients with hypertension. Relationship to tissue Doppler indices of diastolic relaxation / M. H. Tayebjee [et al.]. Am J Hypertens. 2004 Sep;17(9):770-4.
       10. Kurrelmeyer KM, Ashton Y, Xu J, Nagueh SF, Torre-Amione G, Deswal A. Effects of spironolactone treatment in elderly women with heart failure and preserved left ventricular ejection fraction / K. M. Kurrelmeyer [et al.]. J Card Fail. 2014 Aug;20(8):560-8.
11. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2014. Available from: http://www.goldcopd.org.
12. Mancia G, Fagard R, Narkiewicz K, Redón J, Zanchetti A, Böhm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A, Galderisi M, Grobbee DE, Jaarsma T, Kirchhof P, Kjeldsen SE, Laurent S, Manolis AJ, Nilsson PM, Ruilope LM, Schmieder RE, Sirnes PA, Sleight P, Viigimaa M, Waeber B, Zannad F. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013 Jul;31(7):1281-357.
13. State Institution Prof. M. I. Sytenko Institute of Pathology of Spine and Joints of NAMCU Kharkov State Zooveterynaryc Academy ; Leontyeva FS, Filipenko VA, Timoshenko OP еt al. Patent UА 29198 MPC (2006) G 01N 33/48. Method of determination of factions of sulfated hexozaminoglykanes. № u 200708505; request data 24.07.2007; publ. data 26.11.2007. Bull. № 20.
       14. Goriachkovsky AM. Klinicheskaia biokhimiia [Clinical biochemistry]. 2-e izd., ispr. i dop. Odessa, Ukraina: Astroprint; 1998. 608 р.
       15. Levchenko VІ, Novozhitska YuM, Sakhniuk VV. ta іn. Bіokhіmіchnі metodi doslіdzhennia krovі khvorikh [Biochemical methods of a blood analysis of patients]: мetodichnі rekomendatsії dlia lіkarіv khіmіko-toksikologіchnikh vіddіlіv derzhavnikh laboratorіi veterinarnoї meditsini Ukraїni. Kiev, Ukraina: Raiduga; 2004. 104 р.
       16. Delevska VYu. Faktori fіbrozu ta degradatsії ekstratseliuliarnogo matriksa v remodeliuvannі mіokarda lіvogo shlunochka u khvorikh na khronіchne obstruktivne zakhvoriuvannia legen' v spoluchennі z arterіal'noiu gіpertenzієiu [Factors of a fibrosis and degradation of an extracellular matrix in remodeling of a myocardium of a left ventricle at patients with a chronic obstructive disease of lungs in combination with arterial hypertension]. Vіsnik mors'koї meditsini. 2014;(3-4):25-31.
       17. Yabluchanskiy A, Ma Y, Iyer RP, Hall ME, Lindsey ML. Matrix Metalloproteinase-9: Many Shades of Function in Cardiovascular Disease. Physiology (Bethesda). 2013 Nov;28(6):391-403.
       18. Zervoudaki A, Economou E, Stefanadis C, Pitsavos C, Tsioufis K, Aggeli C, Vasiliadou K, Toutouza M, Toutouzas P. Plasma levels of active extracellular matrix metalloproteinases 2 and 9 in patients with essential hypertension before and after antihypertensive treatment. J Hum Hypertens. 2003 Feb;17(2):119-24.
       19. Phatharajaree W, Phrommintikul A, Chattipakorn N. Matrix metalloproteinases and myocardial infarction. Can J Cardiol. 2007 Jul;23(9):727-33.
       20. Kalela A, Koivu TA, Sisto T, Kanervisto J, Höyhtyä M, Sillanaukee P, Lehtimäki T, Nikkari ST. Serum matrix metalloproteinase-9 concentration in angiographically assessed coronary artery disease. Scand J Clin Lab Invest. 2002;62(5):337-42.
       21. Blankenberg S, Rupprecht HJ, Poirier O, Bickel C, Smieja M, Hafner G, Meyer J, Cambien F, Tiret L. Plasma concentrations and genetic variation of matrix metalloproteinase 9 and prognosis of patients with cardiovascular disease. Circulation. 2003 Apr;107(12):1579-85.
       22. Ye ZX, Leu HB, Wu TC, Lin SJ, Chen JW. Baseline serum matrix metalloproteinase-9 level predicts long term prognosis after coronary revascularizations in stable coronary artery disease. Clin Biochem. 2008 Mar;41(4-5):292-8.
       23. Onal IK, Altun B, Onal ED, Kirkpantur A, Gul Oz S, Turgan C. Serum levels of MMP-9 and TIMP-1 in primary hypertension and effect of antihypertensive treatment. Eur J Intern Med. 2009 Jul;20(4):369-72.
       24. Ceron CS, Castro MM, Rizzi E, Montenegro MF, Fontana V, Salgado MC, Gerlach RF, Tanus-Santos JE. Spironolactone and hydrochlorothiazide exert antioxidant effects and reduce vascular matrix metalloproteinase-2 activity and expression in a model of renovascular hypertension. Br J Pharmacol. 2010 May;160(1):77-87.
       25. Rude MK, Duhaney TA, Kuster GM, Judge S, Heo J, Colucci WS, Siwik DA, Sam F. Aldosterone stimulates matrix metalloproteinases and reactive oxygen species in adult rat ventricular cardiomyocytes. Hypertension. 2005 Sep;46(3):555-61.

Поиск по сайту