Department for Cardiovascular Research (DCR)

 

For years, DCR has been dealing with studying the of mechanisms of cardiovascular system regulation in physiological and pathological conditions. The founder of the Department, MD ScD Kentera Dušan, Research Professor, began studies of arterial and pulmonary hypertension (in terms of pulmonary hypoxia) until the end of the eighties when the research field has been expanded to the area of acute and the chronic renal failure.

            Prevalence of hypertension, atherosclerosis, cerebrovascular, and renal diseases, directed our research towards clarification of the role of nitric oxide (NO), endothelin, renin-angiotensin system, and endogenous antioxidants (first line of the endogenous defense in response to oxidative stress) in the pathogenesis and progression of these disorders.

            Nowadays, the focus of DCR are natural and synthetic antihypertensive drugs, antioxidants, and lipid-lowering drugs, and these researches are conducted in three research laboratories:

  1. Laboratory for Experimental Hypertension,
  2. Laboratory for Experimental Nephrology and
  3. Laboratory for Experimental Biochemistry and oxidative stress.

            All studies are conducted in accordance with the Animal Welfare Act. Strains of rats, normotensive Wistar rats, and spontaneously hypertensive (SHR) rats, are bred at the Vivarium of the Institute for Medical Research, University of Belgrade.

            Experimental models of human diseases studied in our Department include model of essential hypertension (SHR, Okamoto-Aoki strain that exposed a genetically determined hypertension), model of malignant hypertension, acute renal failure model (ischemia-reperfusion-induced renal injury), and model of pharmacologically and surgically induced focal segmental glomerulosclerosis, and ageing/hypertension induced progressive renal failure.

            Haemodynamic parameters which are evaluated are systolic blood pressure and heart rate which are measured indirectly (Physiograph Four Narco Biosystem USA); direct measurement of systolic, diastolic, mean blood pressure, cardiac output and heart rate (physiological data acquisition system, 9800TCR Cardiomax III-TCR Thermodilution Cardiac Output for mice, rats and large subjects (Columbus Instruments', Columbus, OH, USA); registration of regional blood flow (Transonic T106 Small Animal Flowmeter, Transonic System Inc., Ithaca, New York).

            Assessment of renal function is performed by measuring creatinine and urea concentrations in plasma and urine (COBAS INTEGRA 400 plus, Hoffmann-La Roche, Germany) and their clearances estimation; determining of electrolyte and protein in urine and plasma and their excretion estimation; determination of water retention);

            For the assessment of lipid profile, we determine plasma cholesterol (TC), high molecular density cholesterol (HDL-C) and triglycerides (TRG) by an automated analyzer (COBAS INTEGRA 400 plus, Hoffmann-La Roche, Germany);

            For the evaluation of oxidative status, we measure the production of NO metabolites and lipid peroxidation (TBARS) in plasma and tissue, as well as measurement of the activities and concentrations of antioxidant enzymes in red blood cells and other tissues such as: catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxidase (GPx), and antioxidant capacity of plasma and other tissues.

Сарадници - Група за кардиоваскуларну физиологију

др Ђурђица Јововић, НСАВ (руководилац групе)

др Зоран Милорадовић, НСАВ

др Невена Михаиловић-Станојевић, НСАВ

др Јелица Грујић Милановић, виши научни сарадник

др Милан Иванов, виши научни сарадник

Данијела Карановић, истраживач сарадник

Уна Јована Вајић, истраживач сарадник

PROJECTS

Заменик за крв (сарадња са привредом)

Пословно-техничка сарадња ИМИ са Хемофарм Концерном 1996-2000

Investigation of antihypertensive influence of heparin (Међународни пројекат)

Project Leader: Dusan Kentera, MD PhD

International project: USA-Yug Joint Board Scientific Cooperation, 1986-1989.

Карактеризација састава екстракта изолованих из биљака фамилије Ламиацеае и испитивање њиховог антиоксидативног, антилипемичког и антихипертензивног деловања in vivo ​​(Билатерални пројекat)

Руководилац пројекта: Невена Михаиловић-Станојевић

Пројекат бр 69-00-49/2010-02 у оквиру научно-технолошке сарадње између Републике Хрватске и Републике Србије, 2011-2012.

Улога азотног моноксида, слободних радикала и ангиотензина II у структури и функцији крвних судова у моделу експерименталне хипертензије ​ (Билатерални пројекat)

Руководилац пројекта: Зоран Милорадовић
Пројекат бр СК-СРБ-0026-29 у оквиру научно-технолошке сарадње између Републике Словачке и Републике Србије, 2010-2011.

Физиологија плућног крвотока​ (Национални пројекat)

Руководилац пројекта: Душан Кентера, научни саветник

Основна истраживања: 1970

Хемодинамске промене у току хипокалоријске исхране​ (Национални пројекat)

Руководилац пројекта: Влатко Вељковић,

Основна истраживања: 1971-1975

Xемодинамика плућног крвотока​ (Национални пројекat)

Руководилац пројекта: Душан Кентера, научни саветник

Основна истраживања: 971-1975

Механизми неких хомеостатских реакција крвотока​ (Национални пројекat)

Руководилац пројекта: Душан Кентера, научни саветник

Основна истраживања: 1976-1980

Деловање дихидроергозина на кардиоваскуларни систем паса​ (Национални пројекat)

Руководилац пројекта: Душан Кентера, научни саветник

Основна истраживања: 1980

Хомеостатска контрола притиска у системском и плућном крвотоку ​ (Национални пројекat)

Руководилац пројекта: Душан Кентера, научни саветник

Основна истраживања: 1981-1985

Улога ендокриних чинилаца из сржи бубрега у регулацији артериског притиска ​ (Национални пројекat)

Руководилац пројекта: Динко Сушић, научни саветник

Основна истраживања: 1984 -1985

Хомеостаза системског и плућног крвотока ​ (Национални пројекat)

Руководилац пројекта: Душан Кентера, научни саветник

Основна истраживања: 1986-1990

Хипертензивни и антихипертензивни механизми у плућној системској циркулацији (Национални пројекat)

Руководилац пројекта: Динко Сушић, научни саветник

Основна истраживања: Министарство науке Републике Србије 1991-1995

Испитивање ендогених фактора који учествују у регулацији крвног притиска и функција бубрега (Национални пројекat)

Испитивање ендогених фактора који учествују у регулацији крвног притиска и функција бубрега у оквиру пројекта „Клиничке и експерименталне студије хипертензије и регулаторних механизама“

Експериментални модели у истраживању патофизиолошких механизама кардиоваскуларних и бубрежних обољења ​ (Национални пројекat)

Руководилац пројекта: Ђурђица Јововић, научни саветник

Основна истраживања: Министарство науке и технолошког развоја Републике Србије, M 1756, 2002-2005.

Улога биолошки активних молекула у моделима кардиоваскуларних и бубрежних обољења (Национални пројекat)

Руководилац пројекта: Ђурђица Јововић, научни саветник

Основна истраживања: Министарство науке и технолошког развоја Републике Србије, O 145054, 2006-2010.

Испитивање улоге активних компоненти Thymus serpyllum L. и Urtica dioica L. са подручја Србије у експерименталним моделима кардиоваскуларних обољења (Национални пројекat)

Испитивање улоге активних компоненти Thymus serpyllum L. и Urtica dioica L. са подручја Србије у експерименталним моделима кардиоваскуларних обољења, у оквиру пројекта ИИИ 46010 „Развој нових инкапсулационих и ензимских технологија за производњу биокатализатора и биолошки активних компонената хране у циљу повећања конкурентности, квалитета и безбедности“

Испитивање антихипертензивног и ренопротективног потенцијала супстанци природног и синтетског порекла у експерименталним моделима кардиоваскуларних и бубрежних обољења (Национални пројекat)

Руководилац пројекта: Ђурђица Јововић, научни саветник

Основна истраживања: Министарство просвете, науке и технолошког развоја Републике Србије, ON 175096, 2011-2017.

Истраживачки радови

The mechanisms of the antihypertensive action of heparin in spontaneously hypertensive rats

Jovović Đ, Jerkić M, Varagić J, Veljković V, Miloradović Z, Marijan M, Sušić D (1997): The mechanisms of the antihypertensive action of heparin in spontaneously hypertensive rats. Acta Vet 47: 211-220.

L-Arginine reduces tubular cell injury in acute postischemic renal failure

Jerkić M, Varagić J, Jovović Đ, Radujković-Kuburović G, Nastić-Mirić D, Adanja-Grujić G, Marković-Lipkovski J, Dimitrijević J, Miloradović Z, Vojvodić SB (1999): L-Arginine reduces tubular cell injury in acute postischemic renal failure. Nephrol Dial Transplant 14: 1398-1407.

The effects of endothelin receptor blockade in the course of experimental postischaemic acute renal failure

Miloradović Z, Jerkić M, Jovović Đ, Mihailović Stanojević N, Stošić G, Marković-Lipkovski J (2002): The effects of endothelin receptor blockade in the course of experimental postischaemic acute renal failure. Acta Vet: 52 (2-3): 137-150.

Relative roles of endothelin-1 and angiotensin II in experimental post-ischaemic acute renal failure

Jerkić M, Miloradović Z, Jovović Đ, Mihailović-Stanojević N, Elena JV, Nastić-Mirić D, Grujić-Adanja G, Rodriguez-Barbero A, Marković-Lipkovski J, Vojvodić SB, Manero MV, Prieto MP, Lopez-Novoa JM (2004): Relative roles of endothelin-1 and angiotensin II in experimental post-ischaemic acute renal failure. Nephrol Dial Transplant 19: 83-94.

Influence of carvedilol on chronic renal failure progression in spontaneously hypertensive rats with adriamycin nephropathy

Jovanović D, Jovović Đ, Mihailović-Stanojević N, Miloradović Z, Dimitrijević J, Maksić N, Đukanović L (2005): Influence of carvedilol on chronic renal failure progression in spontaneously hypertensive rats with adriamycin nephropathy. Clin Nephrol 63(6): 446-453.

Allopurinol and enalapril failed to conserve urinary NOx and sodium in ischemic acute renal failure in spontaneously hypertensive rats

Radovic M, Miloradovic Z, Popovic T, Mihailovic-Stanojevic N, Jovovic D, Tomovic M, Colak E, Simic-Ogrizovic S, Djukanovic L (2006): Allopurinol and enalapril failed to conserve urinary NOx and sodium in ischemic acute renal failure in spontaneously hypertensive rats. Am J Nephrol 26: 388-399.

The effects of endothelin and L-NAME on plasma uric acid and urea concentration in Wistar rats

Popović T, Jovović Đ, Miloradović Z, Mihailović-Stanojević N, Spasić M (2006): The effects of endothelin and L-NAME on plasma uric acid and urea concentration in Wistar rats. Acta Vet 56 (2-3): 181-189.

The effects of iron-containing superoxide dismutases on haemodynamic parameters in spontaneously hypertensive rats

Aleksić T, Jovović Đ, Miloradović Z, Mihailović-Stanojević N, Grujić-Milanović J, Spasić M (2006): The effects of iron-containing superoxide dismutases on haemodynamic parameters in spontaneously hypertensive rats. Acta Physiol Hung. 93(4): 285-292.

Effects of rapamycin on active Heymann nephritis

Naumovic R, Jovovic D, Basta-Jovanovic G, Miloradovic Z, Mihailovic-Stanojevic N, Aleksic T, Jovanovic D (2007): Effects of rapamycin on active Heymann nephritis. Am J Nephrol 27: 379-89.

Bosentan and losartan ameliorate acute renal failure associated with mild but not strong NO blockade

Miloradovic Z, Jerkic M, Jovovic D, Mihailovic-Stanojevic N, Milanovic JG, Stosic G, Markovic-Lipkovski J (2007): Bosentan and losartan ameliorate acute renal failure associated with mild but not strong NO blockade. Nephrol Dial Transplant 22: 2476-2484.

Effects of long-term losartan and L-arginine treatment on haemodinamics, glomerular filtration, and SOD activity in sponaneuosly hypertensive rats

Miloradović Z, Jovović Đ, Mihailović-Stanojević N, Grujić-Milanović J, Milanović S (2008): Effects of long-term losartan and L-arginine treatment on haemodinamics, glomerular filtration, and SOD activity in sponaneuosly hypertensive rats. Can J Physiol 86: 210-214.

Effects of angiotensin II type-1 receptor blocker losartan on age-related cardiovascular risk in spontaneously hypertensive rats

Mihailović-Stanojević N, Miloradović Z, Grujić-Milanović J, Ivanov M, Jovović Đ (2009): Effects of angiotensin II type-1 receptor blocker losartan on age-related cardiovascular risk in spontaneously hypertensive rats. Gen Physiol Biophys Special Issue 28: 112–118.

Comparative effects of L-arginine and vitamin C pretreatment in SHR with induced postischemic acute renal failure

Miloradović Z, Mihailović-Stanojević N, Grujić-Milanović J, Ivanov M, Kuburović G, Marković-Lipkovski J, Jovović Đ (2009): Comparative effects of L-arginine and vitamin C pretreatment in SHR with induced postischemic acute renal failure. Gen Physiol Biophys Special Issue 28: 105–111.

Effect of carvedilol on pulse pressure and left ventricular hypertrophy in spontaneously hypertensive rats with adriamycin nephropathy

Jovanović D, Jovovic Đ, Mihailović-Stanojević N, Miloradović Z, Naumović R, Dimitrijevic J, Maksić N, Đukanovic L (2009): Effect of carvedilol on pulse pressure and left ventricular hypertrophy in spontaneously hypertensive rats with adriamycin nephropathy. Biomed Pharmacother 63(8): 571-576

Reduced progression of adryamicin nephropathy in spontaneously hypertensive rats treated by losartan

Mihailović-Stanojević N, Jovović Đ, Miloradović Z, Grujić-Milanović J, Jerkić M, Marković-Lipkovski J (2009): Reduced progression of adryamicin nephropathy in spontaneously hypertensive rats treated by losartan. Nephrol Dial Transplant 24: 1142-50.

Chronic Changes of Hematocrit Value Alter Blood Pressure and Glomerular Filtration in Spontaneously Hypertensive Rats.

Milanović S, Jovović Đ, Mihailović-Stanojević N, Grujić-Milanović J,. Ivanov M, Karanović D, and Miloradović Z (2012): Chronic Changes of Hematocrit Value Alter Blood Pressure and Glomerular Filtration in Spontaneously Hypertensive Rats. Acta Vet 62 (1): 27-37.

Antioxidant and Antihypertensive Activity of Extract from Thymus serpyllum L. in Experimental Hypertension

Mihailovic-Stanojević N, Belsčak-Cvitanović A, Grujić-Milanović J, Ivanov M, Jovović Đ, Bugarski D, Miloradović Z (2013): Antioxidant and Antihypertensive Activity of Extract from Thymus serpyllum L. in Experimental Hypertension. Plant foods for human nutrition 68(3): 235-240.

Losartan improved antioxidant defense, renal function and structure of postischemic hypertensive kidney.

Ivanov M, Mihailović-Stanojević N, Grujić Milanović J, Jovović Dj, Marković-Lipkovski J, Ćirović S, Miloradović Z (2014): Losartan improved antioxidant defense, renal function and structure of postischemic hypertensive kidney. Plos One, May 2014, 9(5):e96353. doi: 10.1371/journal.pone.0096353. eCollection

Prevention of systemic and regional haemodynamic alterations, hypercreatininemia, hyperuremia and hyperphosphatemia by losartan in hypertension with acute renal failure.

Ivanov M, Mihailović-Stanojević N, Grujić-Milanović J, Jovović Đ. and. Miloradović Z (2011): Prevention of systemic and regional haemodynamic alterations, hypercreatininemia, hyperuremia and hyperphosphatemia by losartan in hypertension with acute renal failure. Acta Physiol Hung 98: 1-7.

Nitric oxide supplementation in postischemic acute renal failure: normotension versus hypertension

Miloradović Z, Mihailović-Stanojević N, Grujić-Milanović J, Ivanov M., Jerkić M.and Jovović Đ (2011): Nitric oxide supplementation in postischemic acute renal failure: normotension versus hypertension. Curr Pharm Biotechnol 12: 1364-1367.

Acute superoxide radical scavenging reduces blood pressure but does not influence kidney function in hypertensive rats with postischemic kidney injury.

Miloradović Z, Ivanov M, Mihailovic-Stanojević N, Grujić-Milanović J, Jovović Dj, Vajić UJ, Marković-Lipkovski J (2014): Acute superoxide radical scavenging reduces blood pressure but does not influence kidney function in hypertensive rats with postischemic kidney injury. Bio Med Research International (formerly titled Journal of Biomedicine and Biotechnology) 2014 (ID 512619): 8 pages.

Effects of high dose olive leaf extract on haemodynamic and oxidative stress parameters in normotensive and spontaneously hypertensive rats

Dekanski D, Mihailović-Stanojević N, Grujić Milanović J, Jovović Dj, Miloradović Z (2014) Effects of high dose olive leaf extract on haemodynamic and oxidative stress parameters in normotensive and spontaneously hypertensive rats. J Serb Chem Soc 79 (9): 1085–1097.

Vibroacustic microvibrations enhance kidney blood supply, glomerular filtration and glutathione peroxidase activity in spontaneously hypertensive rats

Miloradović Z, Mihailović-Stanojević N, Jovović Đ, Ivanov M, Vajić UJ, Karanović D, Grujić Milanović J (2015): Vibroacustic microvibrations enhance kidney blood supply, glomerular filtration and glutathione peroxidase activity in spontaneously hypertensive rats. Gen Physiol Biophys 34(1):89-94.

Effects of Single and Combined Losartan and Tempol Treatments on Oxidative Stress, Kidney Structure and Function in Spontaneously Hypertensive Rats with Early Course of Proteinuric Nephropathy.

Karanović D, Grujić-Milanović J, Miloradović Z, Ivanov M, Jovović Đ, Vajić UJ, Životić M, Marković-Lipkovski J, Mihailović-Stanojević N (2016): Effects of Single and Combined Losartan and Tempol Treatments on Oxidative Stress, Kidney Structure and Function in Spontaneously Hypertensive Rats with Early Course of Proteinuric Nephropathy. PLoS One 2016;11(8):e0161706.

Up-Regulation Of Heme Oxygenase-1 In Response To Wild Thyme Treatment Protects Against Hypertension And Oxidative Stress

Mihailović-Stanojević N, Miloradović Z, Ivanov M, Bugarski B, Jovović Đ, Karanovic D, Vajić UJ, Komes D, Grujić Milanović J (2016): Up-Regulation Of Heme Oxygenase-1 In Response To Wild Thyme Treatment Protects Against Hypertension And Oxidative Stress. Oxid Med Cell Longev 2016: 1458793.

Angiotensin 2 type 1 receptor blockade different affects postishemic kidney injury in normotensive and hypertensive rats.

Miloradović Z, Ivanov M, Jovović Đ, Karanović D, Vajić UJ, Marković-Lipkovski J, Mihailović-Stanojević N, Milanović JG (2016): Angiotensin 2 type 1 receptor blockade different affects postishemic kidney injury in normotensive and hypertensive rats. J Physiol Biochem 72 (4): 813-820.

Combined angiotensin II type-1 receptor blockade and superoxide anion scavenging affect the post-ischemic kidney in hypertensive rats.

Ivanov M, Mihailović-Stanojević N, Marković-Lipkovski J, Jovović Đ, Karanović D, Miloradović Z, Grujić-Milanović J (2016): Combined angiotensin II type-1 receptor blockade and superoxide anion scavenging affect the post-ischemic kidney in hypertensive rats. Acta Vet 66 (3): 392-405.

Moderate consumption of alcohol-free red wine provide more beneficial effects on systemic haemodynamics, lipid profile and oxidative stress in spontaneously hypertensive rats than red wine.

Mihailovic-Stanojevic N, Savikin K, Zivkovic J, Zdunic G, Miloradovic Z, Ivanov M, Karanovic D, Vajic UJ,Jovovic D, Grujic-Milanovic J (2016): Moderate consumption of alcohol-free red wine provide more beneficial effects on systemic haemodynamics, lipid profile and oxidative stress in spontaneously hypertensive rats than red wine. Journal of Functional Foods 26:719-730.

The red wine polyphenol, resveratrol improves hemodynamics, oxidative defence and aortal structure in essential and malignant hypertension.

Grujic-Milanovic J, Miloradovic Z, Jovovic Dj, Jacevic V, Milosavljevic I, Milanovic S, Mihailovic-Stanojevic N (2017): The red wine polyphenol, resveratrol improves hemodynamics, oxidative defence and aortal structure in essential and malignant hypertension. Journal of Functional Foods 34: 266-276

Тезе