Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2013; 59(3): 39-49


The effect of amlodipine, bisoprolol on the myocardial ultrastructure of the hypertensive rats

Puzyrenko AM, Chekman IS, Kuftyreva TP, Horchakova NO

  1. National O.O. Bogomolets Medical University, Department of Pharmacology, Kyiv, Ukraine
  2. Institute of Problems of Pathology of National O.O. Bogomolets Medical University, Department of Electron Microscopy, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz59.03.039


Abstract

Calcium channel blockers and beta1-adrenoblockers are effective antihypertensive agents, but their cell protective properties are not investigated well. Spontaneously hypertensive rats received a 10 mg/kg/day amlodipine dose and 25 mg/kg/day bisoprolol dose via an orogastric tube during three months. We performed examination of the myocardium's fragments under a scanning electron microscope. Morphometric investigation of mitochondrions we performed using special program what is named "ORGANELLE". Amlodipine significantly normalizes the ultrastructure of the myocardium. This antihypertensive drug prevented the signs of over-contractility of myofibrils. Amlodipine causes the fusion mitochondrions which has compensatory character on the background of good safety of mitochondrial ultrastructures. Another feature of amlodipine is a significant increase in the number of capillaries. Bisoprolol significantly reduced over-contractility of the myofibrils, but the signs of dystrophic-destructive processes in myofibrils and mitochondrions of cardiomyocytes remained. Bisoprolol improved the condition of the endothelial cells, but the activation of the functional activity of these cells has not been observed. The combined use of two antihypertensive drugs amlodipine and bisoprolol led to a better recovery of myofibrils than their separate use, whereas the effect on mitochondrions noted similar as in the group of rats received bisoprolol and that effect was worse than during amlodipine's monotherapy. Also we didn't reveal a reason to combine these drugs after analysis of the effect of the drug combination on the conditions of blood microvessels, which number was increased compared with hypertensive rats, but significantly less than when rats received only amlodipine. These essential cell-protective effects of amlodipine and bisoprolol in spontaneously hypertensive rats could be a significant additional factor in the treatment of hypertension complicated with pathological changes in the heart.

Keywords: hypertension, amlodipine, bisoprolol, ultrastructureof cardiomyocytes, mitochondrions, blood vessels.

References

  1. Zapadnyuk I.V., Zapadnyuk V.I., 3axapiev K.a. Laboratornie zhivotnie. Razvedenie, soderzhanie, ispol'zo- vanie v eksperimente. K.: Vischa shkola, 1983. 383 s.
  2.  
  3. Karupu V.Ya. Elektronnaya mikroskopiya. K.: Vischa shkola, 1984. 208 s.ziologicheskii analiz faktorov riska arterial'noi gipertenzii i ateroskleroza. Novosibirsk, 1992. 72 s.
  4. Markel' A.L., Maslova L.N., Shishkina G.T. Patofiziologicheskii analiz faktorov riska arterial'noi gipertenzii i ateroskleroza.  Novosibirsk, 1992.  72 s.
  5. Puzirenko a.M., Zagorodnii M.I., Gorchakova N.O. ?-adrenoblokatori: suchasni kliniko-farmakologichni aspekti zastosuvannya v medichnii praktitsi . Ukr. nauk.-med. molod. zhurn. 2012. N 1. S. 9-12.
  6.  
  7. Puzirenko a.M., Gorchakova N.O., CHekman I.S. Dovgan' R.S. Suchasni kliniko-farmakologichni aspekti zasto- suvannya blokatoriv kal'tsievih kanaliv v medichnii praktitsi . Tas samo. N 3. S. 30-34.
  8.  
  9. Ribolovlev YU.R., Ribolovlev R.S. Dozirovanie ve- schestv dlya mlekopitayuschih po konstantam biologi- cheskoi aktivnosti . Dokl. aN SSS R. 1979. N 6. S. 1513-1516.
  10.  
  11. Chan D. Mitochondrial fusion and fission in mammals . Annu. Rev. Cell. Dev. Biol. . 2006. 22. P. 79-99. CrossRef PubMed
  12.  
  13. Chen H., Vermulst M., Wang Y.E., Chomyn A., Prolla T.A., McCaffery J.M., Chan D.C. Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutations . Cell. . 2010. 14(2). . P. 280-289. CrossRef PubMed PubMedCentral
  14.  
  15. Choi S.M., Kim J.E., Ahn B.O. Effects of amlodipine orotate on hypertension-related complications in spontaneously hypertensive rats . Arzneimittelforschung. . 2006. 56, 1. . P. 12-17.
  16.  
  17. Hazama F., Ozaki T., Amano S. Scanning electron microscopic study of endothelial cells of cerebral arteries from spontaneously hypertensive rats . Stroke. . 1979. 10(3). P. 245-52. CrossRef PubMed
  18.  
  19. Khan N.A., Chattopadhyay P., Abid M., Pawdey A., Kishore K., Wahi A.K. Protective effects of amlodipine on mitochondrial injury in ischemic reperfused rat heart . J. Environ. Biol. . 2012. . 33(3). P. 591-595. PubMed
  20.  
  21. Kizhakekuttu T.J., Wang J., Dharmashankar K., Ying R., Gutterman D.D., Vita J.A., Widlansky M.E. Adverse alterations in mitochondrial function contribute to type 2 diabetes mellitus-related endothelial dysfunction in humans . Arterioscler. Thromb. Vas.c Biol. . 2012. 32(10). P. 2531-2539. CrossRef PubMed PubMedCentral
  22.  
  23. Lee Y.J., Choi D.H., Cho G.H., Kim J.S., Kang D.G., Lee H.S. Arctium lappa ameliorates endothelial dysfunction in rats fed with high fat/cholesterol diets . BMC Complement. Altern. Med. 2012. 12(1). . P. 116. CrossRef PubMed PubMedCentral
  24.  
  25. Lu J.C., Cui W., Zhang H.L. Additive beneficial effects of and atorvastatin in reversing advanced cardiac hypertrophy in elderly spontaneously hypertensive rats . Clin. Exp. Pharmacol. Physiol. . 2009. . 36, 11. . P. 1110-1119.
  26.  
  27. Mozdy A., Shaw J. A fuzzy mitochondrial fusion apparatus comes into focus . Nat. Rev. Mol. Cell Biol. 2003. . 4(6). P. 468-478. CrossRef PubMed
  28.  
  29. Mougenot N., M"Ђdiani O., Lechat P.Bisoprolol and hydrochlorothiazide effects on cardiovascular remodeling in spontaneously hypertensive rats . Pharmacol. Res. . 2005. 51, 4. . P. 359-365.
  30.  
  31. Nishio M., Sakata Y., Mano T. Beneficial effects of bisoprolol on the survival of hypertensive diastolic heart failure model rats . Eur. J. Heart. Fail. 2008. 10, N 5. P. 446-453. CrossRef PubMed
  32.  
  33. Puzyrenko A.M., Chekman I.S., Kuftyreva T.P., Gorchakova N.O. The effect of amlodipine on the myocardial ultrastructure of the hypertensive rats . J. Int. Scien. Publications. . 2012. 6. P. 351-358.
  34.  
  35. Sanaei-Zadeh H. Treatment of amlodipine overdose . Indian. J. Crit. Care Med. . 2012. 16. P. 182. CrossRef PubMed PubMedCentral
  36.  
  37. Sag C., Yokusoglu M., Cincik M., Ozkan M., Kayir H., Uzun M., Baykal B, Ozogul C., Baysan O., Uzbay I.T. The prevention of myocardial ultrastructural changes by perindopril, atenolol and amlodipine in chronic alcohol administered rats . Pharmacol. Res. . 2006. . 53(2). P. 142-148. CrossRef PubMed
  38.  
  39. Sorop O., Bakker E.N., Pistea A., Spaan J.A., VanBavel E. Calcium channel blockade prevents pressure-dependent inward remodeling in isolated subendocardial resistance . Amer. J. Physiol. Heart. Circ. Physiol. . 2006. . 29(3). P. 1236-1245. CrossRef PubMed
  40.  
  41. Singh A., Bangalore S. Do angiotensin receptor blockers prevent myocardial infarctions as well as other initial therapies? . Curr. Opin. Cadiol. . 2012. 27(4). . P. 381-385. CrossRef PubMed
  42.  
  43. Sun L., Bai Y., Du G. Endothelial dysfunction . an obstacle of therapeutic angiogenesis . Aqeing. Res. Rev. 2009. 8(4). P. 306-313. CrossRef PubMed
  44.  
  45. Statsenko M.E., Derevianchenko M.V. The Place of adrenoblockers in the Treatment of Cardiovascular Disease in Patients With Chronic Obstructive Pulmonary Disease. Kardiologiia. 2012. 52. P. 57-63. PubMed
  46.  
  47. Vesterdal L.K., Mikkelsen L., Folkmann J.K., Sheykhzade M., Cao Y., Roursgaard M., Loft S., Muller P. Carbon black nanoparticles and vascular dysfunction in cultured endothelial cells and artery segments . Toxicol. Lett. 2012. 214(1). P. 19-26. CrossRef PubMed

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2024.