Actuality of hypertension, atherosclerosis, cerebrovascular and renal diseases, directed our investigation towards better clarify 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, as well as their interconnections.
All studies are conducted in accordance with the Animal Welfare Act. We breed the two strains of rats, normotensive Wistar rats and spontaneously hypertensive (SHR) rats, only for own requirements (Vivarium, Institute for Medical Research, University of Belgrade).
Experimental models of human diseases that are 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), model of pharmacologically and surgically induced focal segmental glomerulosclerosis, and ageing/hypertension induced progressive renal failure.
Haemodynamic parameters we evaluate by: indirect blood pressure measurement (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).
For the assessment of lipid profile, we determined plasma cholesterol (TC), high molecular density cholesterol (HDL-C) and triglycerides (TRG) by automated analyzer (COBAS INTEGRA 400 plus, Hoffmann-La Roche, Germany);
For the examination of oxidative stress we follow the production of NO metabolites and production of reactive oxygen radicals (TBARS) in plasma and tissue, as well as, measure the activity of oxidative enzymes in red blood cells and tissue such as: catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GSH).
PROJECTS & EDUCATION
- 1986-1989 Investigation of antihzpertenzive influence of heparin- funded by USA Yug Joint Board Scientific Cooperation
- 1991-1995 Hypertensive and antihypertensive mechanisms in pulmonary and systemic circulation- funded by the Ministry of Science R Serbia
- 1996-2000 “Replacement of hemoglobin-based blood” and “Development of production technology of fat emulsion for parenteral use and liposomes for topical application in a semi industrial plant” funded by the Hemofarm Concern
- 1996-1999 “Investigation of endogenous factors involved in the regulation of blood pressure and kidney function” funded by the Ministry of Science and Technological Development (MSTD) R Serbia
- 2002-2005 Experimental models in the study of pathophysiological mechanisms of cardiovascular and renal diseases- funded by the Ministry of Science and Envarment R Serbia
- 2006-2010 The role of biologically active molecules in experimental models of cardiovascular disease- funded by the MSTD R Serbia
- 2010-2011 scientific-technological cooperation R. Serbia and R Slovakia “The role of nitric oxide, free radicals and angiotensine II in the structure and function of blood vessels in a model of experimental hypertension”
- 2011-2012, “Characterization of the composition of extracts isolated from plants of the family Lamiaceae and investigation of their antioxidant, antihypertensive and antilipemic effects in vivo “, funded by Serbia-Croatia Bilateral Scientific Collaboration
- 2011-, subproject “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” in the project “Development of new incapsulation and enzyme technology for the production of biocatalysts and bioactive food components to increase its competitiveness, quality and safety”, funded by the МES Republic of Serbia.
- 2011- ’’Investigation of antihypertensivе and renoprotectivе potential of natural and synthetic compounds in the experimental models of cardiovascular and renal diseases“, funded by the МES Republic of Serbia
- Miloradovic Z, Mihailovic-Stanojevic NF, Jovovic DF, Ivanov MF, Vajic UJ FAU – Karanovic D, Karanovic DF, Grujic MJ: Vibroacustic microvibrations enhance kidney blood supply, glomerular filtration and glutathione peroxidase activity in spontaneously hypertensive rats. General Physiology and Biophysics, 11/2014; DOI: 10.4149/gpb_2014033
- Ivanov M, Mihailovic-Stanojevic N, Grujic Milanovic J, Jovovic D, Markovic-Lipkovski J, Cirovic S, Miloradovic Z. Losartan improved antioxidant defense, renal function and structure of postischemic hypertensive kidney. PloS one, 9(5):e96353, 2014, doi:10.1371/journal.pone.0096353,
- Miloradovic Z, Ivanov M, Mihailovic-Stanojevic N, Grujic Milanovic J, Jovovic Dj, Markovic-Lipkovski J and Vajic UJ. Acute Superoxyde Radical Scavenging Reduces Blood Pressure but does not Improve Kidney Function in Hypertensive Rats with Postischemic Kidney Injury. BioMed Research International, doi:10.1155/2014/512619, 2014. IF=2.880, 50/160
- Mihailovic-Stanojevic N, Belscak-Cvitanovic A, Grujic-Milanovic J, Ivanov M, Jovovic D, Bugarski D, Miloradovic Z. Antioxidant and Antihypertensive Activity of Extract from Thymus serpyllum L. in Experimental Hypertension. Plant foods for human nutrition. Sep;68(3):235-240, 2013,
- Miloradović Z, Mihailović-Stanojević N, Grujić-Milanović J, Ivanov M., Jerkić M, Jovović D. Nitric oxide supplementation in postischemic acute renal failure: normotension versus hypertension. Curr. Pharm. Biotechnol. 12 , 1364-1367, 2011.
- Mihailović-Stanojević N, Jovović Đ, Miloradović Z, Grujić-Milanović J, Jerkić M, Marković-Lipkovski J. Reduced progression of adryamicin nephropathy in spontaneously hypertensive rats treated by losartan. Nephrol.Dial.Transplant 24:1142-50, 2009.
- Naumović R, Jovović D, Basta-Jovanović G, Miloradović Z, Mihailović-Stanojević N, Aleksić T et al. Effects of rapamycin on active Heymann nephritis. Am J Nephrol 27:379-89. 2007. IF=3.164, 12/57
- Miloradović Z, Jerkić M, Jovović D, Mihailović-Stanojević N, Milanović JG, Stošić G et al. Bosentan and losartan ameliorate acute renal failure associated with mild but not strong NO blockade. Nephrol.Dial.Transplant 22:2476-84. 2007. IF=3.568, 11/57
- Radović M, Miloradović Z, Popović T, Mihailović-Stanojević N, Jovović Đ, Tomović M et al. Allopurinol and enalapril failed to conserve urinary NOx and sodium in ischemic acute renal failure in spontaneously hypertensive rats. Am J Nephrol 26:388-99, 2006. IF=2.879, 14/55
- Jerkić M, Miloradović Z, Jovović D, 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. Relative roles of endothelin-1 and angiotensin II in experimental post-ischaemic acute renal failure. Nephrol Dial Transplant 19: 83-94, 2004. IF=2.976, 10/51