Group for Cardiovascular Research (DCR)

 

            The main research interests of this department include current topics in the pathophysiology of experimental hypertension, postischemic acute kidney injury, chronic kidney disease (CKD), and dyslipidemia. Special research focuses are directed to the roles of endothelin peptides, renin-angiotensin-aldosterone system, reactive oxygen species, and oxidative stress. In accordance with the recent trends, the group also investigate polyphenol-rich plant products in the therapy of hypertension, CKD, and dyslipidemia, using the whole plant extract as well as single active components. A special interest of this group is directed to the efficacy of hyperbaric oxygen preconditioning in the model of renal ischemia. These studies 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 performed in this department are in accordance with the Animal Welfare Act. Strains of rats - normotensive Wistar rats and spontaneously hypertensive rats (SHR) are bred at the Vivarium of the University of Belgrade, Institute for Medical Research, National Institute of Republic of Serbia. Experimental models of human diseases studied in this department include a model of essential hypertension (SHR, Okamoto-Aoki strain with genetically determined hypertension), model of malignant hypertension, acute renal failure model (ischemia-reperfusion-induced renal injury), model of pharmacologically and surgically induced focal segmental glomerulosclerosis, and aging/hypertension-induced progressive renal failure. In this department hemodynamic in vivo studies are very often performed and they include indirect blood pressure measurement by tail-cuff method (MRBP system, World Precision Instruments, inc.), direct blood pressure, heart rate, and cardiac output measurements (physiological data acquisition system, 9800TCR Cardiomax III-TCR - thermodilution cardiac output for mice, rats and large subjects, Columbus Instruments), as well as ultrasound measurement of blood flow through different blood vessels (Transonic T106 Small Animal Flowmeter, Transonic System Inc.). For the estimation of the kidney function, appropriate plasma and urine biochemical parameters are measured (Cobas Integra 400 plus analyzer, Hoffmann-La Roche), lipid profile (such as HDL-C, LDL-C, total cholesterol, and triglycerides, Cobas Integra 400 plus analyzer, Hoffmann-La Roche), as well as oxidative stress parameters are determined in many biological tissues and fluids.  Members of this department frequently use molecular diagnostic techniques (ELISA, Western blot, etc.), while in collaboration with other departments and institutions perform pathomorphological and immunohistochemical studies. In addition, many collaborations and Ph.D. theses, mainly from the Biological Faculty University of Belgrade, are based on the research in this laboratory. Members of this group also participated in basic and Ph.D. studies at the Medical Faculty, University of Belgrade, as well as at the Veterinary Faculty, University of Belgrade. Today, the department realizes national projects, collaborates with international research groups, while the members of this department publish in relevant scientific journals and present results on leading national and international meetings. Considering their expertise, investigation of vasoactive properties of newly developed drugs (including their pharmacokinetic/pharmacodynamic studies), as well as drug effects on kidney function and oxidative stress in vivo (especially on SHR) could be a reasonable outcome for further research/collaboration. 

Group for Cardiovascular Research – associates

 

Djurdjica Jovovic, Ph.D., Research Professor (Group Leader)

 

Zoran Miloradovic, Ph.D., Research Professor 

 

Nevena Mihailovic Stanojevic, Ph.D., Research Professor 

 

Jelica Grujic Milanovic, Ph.D., Research Professor

 

Milan Ivanov, Ph.D., Associate Research Professor

 

Danijela Karanovic, Ph.D., Assistant Research Professor

 

Una-Jovana Vajic, Ph.D., Assistant Research Professor

PROJECTS

Replacement of hemoglobin-based blood 

Cooperation with pharmaceutical company "HEMOFARM Koncern" a.d., 1996-2000.

 

Investigation of antihypertensive influence of heparin (International project)

Project Leader: Dusan Kentera, MD Ph.D.

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

 

Characterization of the composition of extracts isolated from plants of the family Lamiaceae and investigation of their antioxidant, antihypertensive and antilipemic effects  in vivo (Bilateral scientific collaboration)

Project Leader: Nevena MIhailovic Stanojevic, Ph.D.

Bilateral scientific collaboration: scientific-technological cooperation between Republic of Serbia and Republic of Croatia, 2011-2012.

The role of nitric oxide, free radicals and angiotensine II in the structure and function of blood vessels in a model of experimental hypertension (Bilateral scientific collaboration)

Project Leader: Zoran Miloradovic, Ph.D.

Bilateral scientific collaboration: scientific-technological cooperation between Republic of Serbia and Slovak Republic, 2010-2011.

 

Physiology of pulmonary circulation (National project)

Project Leader: Dusan Kentera, MD Ph.D.

Basic research, 1970.

Hemodynamic changes in a low-calorie diet (National Project)

Project Leader: Vlatko Veljkovic, MD Ph.D.

Basic research, 1971-1975.

Hemodynamics of pulmonary circulation (National project)

Project Leader: Dusan Kentera, MD Ph.D.

Basic research, 1971-1975.

Homeostasis of systemic and pulmonary circulation (National project)

Project Leader: Dusan Kentera, MD Ph.D.

Basic research, 1986-1990.

Hypertensive and antihypertensive mechanisms in pulmonary and systemic circulation (National project)

Project Leader: Dinko Susic, MD Ph.D.

Basic research, Ministry of Science of Republic of Serbia, 1991-1995.

 

Experimental models in the study of pathophysiological mechanisms of cardiovascular and renal diseases (National Project)

Project Leader: Djurdjica Jovovic, MD Ph.D.

Basic research, Ministry of Science and Technological Development of Republic of Serbia, 2002-2005.

The role of biologically active molecules in experimental models of cardiovascular disease (National Project)

Project Leader: Djurdjica Jovovic, MD Ph.D.

Basic research, Ministry of Science and Technological Development of Republic of Serbia, 2006-2010.

 

Investigation of the role of active components of Thymus serpyllum L. and Urtica dioica L. from the territory of Serbia in experimental models of cardiovascular disease (National Project)

Project Leader: Prof. Branko Bugarski and Prof. Zorica Knezevic Jugovic, University of Belgrade, Faculty of Technology and Metallurgy

Subproject Leader: Nevena Mihailovic-Stanojevic, Ph.D.

Integral and interdisciplinary project, Ministry of Education, Science and Technological Development of Republic of Serbia, 2011-2017.

Investigation of antihypertensivе and renoprotectivе potential of natural and synthetic compounds in the experimental models of cardiovascular and renal diseases (National project)

Project Leader: Djurdjica Jovovic, MD Ph.D.

Basic research, Ministry of Education, Science and Technological Development of Republic of Serbia, 2011-2017.

 

Scientific papers

Excesive consumption of unsaturated fatty acids leads to oxidative and inflammatory instability in Wistar rats

 Grujic-Milanovic J, Miloradovic Z, Mihailovic-Stanojevic N, Banjac V, Vidosavljevic S, Ivanov M, Karanovic D, Vajic U-J, Jovovic Dj. Int J Mol Sci 2021 139: 111691.

https://www.sciencedirect.com/science/article/pii/S075333222100473X

Hyperbaric Oxygen Preconditioning Upregulates Heme OxyGenase-1 and Anti-Apoptotic Bcl-2 Protein Expression in Spontaneously Hypertensive Rats with Induced Postischemic Acute Kidney Injury

Jelena Nesovic Ostojic, Milan Ivanov, Nevena Mihailovic-Stanojevic, Danijela Karanovic, Sanjin Kovacevic, Predrag Brkic, Maja Zivotic, Una Jovana Vajic, Djurdjica Jovovic, Rada Jeremic, Senka Ljubojevic-Holzer, and Zoran Miloradovic. Int J Mol Sci. 2021 22: 1382-1396

https://www.mdpi.com/1422-0067/22/3/1382

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

Theses