Department of Experimental Hypertension

Department of experimental hypertension is focused to the regulatory mechanisms of blood pressure regulation and endothelial (dys)function in prehypertension and various experimental models of human primary hypertension as well as during aging. 

We use integrative and transdisciplinary approaches in order to identify causes and behavioural, functional, metabolic and structural consequences of high blood pressure using various animal models of human hypertension, in various ages, in both male and female subjects. We investigate the involvement of various endothelium-derived factors in condition of hyperuricemia. We look for new approaches in prevention and treatment of hypertension and endothelial dysfunction, which both considerably contribute to development of cardiovascular, metabolic and neuropsychiatric disorders. 

Current projects are focused on the role of hyperuricemia and biogenic iron in development of cardiovascular and behavioural disorders. More about the department… 

 

Head:

RNDr. Iveta Bernátová, DrSc.

tel.: +421 2 3226 6013

e-mail:  Iveta.Bernatova@savba.sk

 

Researchers:

MUDr. RNDr. Angelika Púzserová, PhD.

Mgr. Peter Bališ, PhD.

RNDr. Ima Dovinová, PhD.

Mgr. Michal Kluknavský, PhD.

RNDr. Silvia Líšková, PhD.

 

Undergraduate students:

Bc. Kurjaková (Faculty of Natural Sciences, Comenius University) 

Bc. Andrea Mičurová (Faculty of Natural Sciences, Comenius University) 

 

Research associate:

RNDr. Valéria Regecová

 

Laboratory technician:

Jana Peťová

 


About

Department of experimental hypertension is focused to the regulatory mechanisms of blood pressure regulation and endothelial (dys)function in prehypertension and various experimental models of human primary hypertension as well as during aging. 

We use integrative and transdisciplinary approaches in order to identify causes and behavioural, functional, metabolic and structural consequences of high blood pressure using various animal models of human hypertension, in various ages, in both male and female subjects. We investigate the involvement of various endothelium-derived factors in condition of hyperuricemia. We look for new approaches in prevention and treatment of hypertension and endothelial dysfunction, which both considerably contribute to development of cardiovascular, metabolic and neuropsychiatric disorders. 

Current projects are focused on the role of hyperuricemia and biogenic iron in development of cardiovascular and behavioural disorders.  

Furthermore, we investigate iron metabolism and alterations of its magnetic properties during aging, stress exposure and in process of hypertension development. The aim is to identify the contribution of hyperuricemia to initiation endothelial dysfunction and cardiovascular diseases. The another aim is to determine the relations among aging, iron metabolism and its magnetic properties. We will also investigate the impact of biocompatible ultra-small superparamagnetic iron oxide nanoparticles on blood pressure regulation as well as function of the heart and blood vessels in conditions of normotension and hypertension, respectively.  

In humans, chronic social stress is considered to be a significant risk factor hypertension development. Thus, in addition to the experimental studies mentioned above, we build a database of blood pressure values, heart rate and of somatometric parameters of children and juveniles that documents the developmental trends of blood pressure and somatic parameters in the young Slovak population in the range of 3 – 20 years in the  last 30 years. 

In addition, we cooperate with universities and clinicians on research projects, clinical studies as well as education of students.     

The newest experiments are aimed to mathematical modelling of blood pressure regulation in rats in cooperation with experts in cybernetic from the Faculty of Electrical Engineering and Information Technology, Slovak Technical University in Bratislava and with Institute of Physiology of the Czech Academy of Sciences in Prague, Czech Republic. 

 


Selected publications since 2012

 

BERNÁTOVÁ, Iveta. Endothelial dysfunction in experimental models of arterial hypertension: Cause or consequence? In BioMed Research International, 2014, vol. 2014, article ID 598271, p. 1-14. (2.706 – IF2013)

PÚZSEROVÁ, Angelika – SLEZÁK, Peter – BALIŠ, Peter – BERNÁTOVÁ, Iveta. Long-term social stress induces nitric oxide-independent endothelial dysfunction in normotensive rats. In Stress, 2013, vol.16, no. 3, p. 331-339. (3.252 – IF2012)

GALLEANO, Monica – BERNÁTOVÁ, Iveta – PÚZSEROVÁ, Angelika – BALIŠ, Peter – ŠESTÁKOVÁ, Natália – PECHÁŇOVÁ, Oľga – FRAGA, César G. (-)-Epicatechin reduces blood pressure and improves vasorelaxation in spontaneously hypertensive rats by NO-mediated mechanism. In IUBMB life, 2013, vol. 65, no. 8, p. 710-715. (2.789 – IF2012)

KOPINCOVÁ, Jana – PÚZSEROVÁ, Angelika – BERNÁTOVÁ, Iveta. L-NAME in the cardiovascular system – nitric oxide synthase activator? In Pharmacological Reports, 2012, vol. 64, p. 511-520. (2.445 – IF2011)

HORVÁTHOVÁ, Martina –  ŽITŇANOVÁ, Ingrid – KRALOVIČOVÁ, Zuzana – BALIŠ, Peter – PÚZSEROVÁ, Angelika, MUCHOVÁ, Jana –  KLUKNAVSKÝ, Michal – ĎURAČKOVÁ, Zdenka – BERNÁTOVÁ, Iveta. Sex differences in the blood antioxidant defense system in juvenile rats with various genetic predispositions to hypertension. In Hypertension Research, 2016, doi: 10.1038/hr.2015.117

PÚZSEROVÁ, Angelika – ILOVSKÁ, Veronika – BALIŠ, Peter – SLEZÁK, Peter – BERNÁTOVÁ, Iveta. Age-related alterations in endothelial function of femoral artery in young SHR and WKY rats. In BioMed Research International, 2014, vol. 2014, article ID 658479, p. 1-12. (2.706 – IF2013)

SLEZÁK, Peter – PÚZSEROVÁ, Angelika – BALIŠ, Peter – ŠESTÁKOVÁ, Natália – MAJZÚNOVÁ, Miroslava – DOVINOVÁ, Ima – KLUKNAVSKÝ, Michal – BERNÁTOVÁ, Iveta. Genotype-related effect of crowding stress on blood pressure and vascular function in young female rats. In BioMed Research International, 2014, vol. 2014, article ID 413629, p. 1-11. (2.706 – IF2013)

RADOŠINSKÁ, Jana – BAČOVÁ, Barbara – BERNÁTOVÁ, Iveta – NAVAROVÁ, Jana – ZHUKOVSKA, Anna – SHYSH, Angela – OKRUHLICOVÁ, Ľudmila – TRIBULOVÁ, Narcis. Myocardial NOS activity and connexin-43 expression in utreated and omega-3 fatty acids-treated spontaneously hypertensive and hereditary hypertriglyceridemic rats. In Molecular and Cellular Biochemistry, 2011, vol. 347, no.1-2, p. 163-173. (2.168 – IF2010)

PÚZSEROVÁ, Angelika – TÖRÖK, Jozef – SOTNÍKOVÁ, Ružena – ZEMANČÍKOVÁ, Anna – BERNÁTOVÁ, Iveta. Reactivity of the mesenteric bed arteries of normotensive rats exposed to chronic social stress. In General Physiology and Biophysics, 2012, vol. 31, iss. 3, p. 279-290. (1.192 – IF2011)

LEDVÉNYIOVÁ-FARKAŠOVÁ, Veronika – BERNÁTOVÁ, Iveta – BALIŠ, Peter – PÚZSEROVÁ, Angelika – BARTEKOVÁ, Monika – GABLOVSKÝ, Ivan – RAVINGEROVÁ, Táňa. Effect of crowding stress on tolerance to ischemia/reperfusion injury in young male and female hypertensive rats: molecular mechanisms. In Canadian Journal of Physiology and Pharmacology, 2015, vol. 93, iss. 9, p. 793-802. (1.770 – IF2014)

 


Current projects

International

Study the role of iron oxide nanoparticles in a model of hypertension and comorbid Alzheimer’s disease

partner:  Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria  

principal investigators: Iveta Bernátová, PhD., DSc., Assoc. Prof. Jana Chekalarova, PhD.  

project number: BAV-SAV-18-11  

duration: 1.1. 2018 – 31.12. 2020 

The aim of this research is to identify differences in possible toxic effects of superparamgnetic ultra small iron nanoparticles administered either acutely or repeatedly in normotensive and hypertensive rats with comorbid Alzheimer’s disease.     

 

National

Research of magnetic forms of iron in development of cardiovascular diseases and behavioural disorders 

principal investigator: Iveta Bernátová, PhD., DSc. 

project number: APVV-16-0263 

duration: 1.7.2017 – 30.6.2021  

The aim of this project is to investigate the impact of aging on the metabolism of biogenic iron and its magnetic properties in association with metabolic and functional alterations in the cardiovascular system and brain in rats with various genetic predispositions to hypertension. We will also investigate the impact of exogenously administered iron in the form of the biocompatible ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) on blood pressure regulation and function of the heart and blood vessels in conditions of normotension, chronically increased blood pressure and in conditions of acute stress (i.e. acutely elevated blood pressure). 

 

Effect of ultrasmall superparamagnetic iron oxide nanoparticles on the cardiovascular system of rats with high blood pressure 

principal investigator: Iveta Bernátová, PhD., DSc. 

duration: 1.1.2017 – 31.12.2020 

project number: VEGA 2/0160/17  

This project is aimed to investigate if acute stress and chronic high blood pressure can facilitate the uptake of ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) into the arterial wall and heart, to modify cardiovascular function, including blood pressure regulation and to induce metabolic disorders and oxidative damage in the heart and vasculature. We will also investigate if the L-type of voltage-dependent calcium channels is involved in iron uptake after USPIONs treatment. 

 

Mechanisms involved in uric acid-induced endothelial dysfunction depending on the age and genetic predisposition to hypertension    

principal investigator: Angelika Púzserová, MD, PhD. 

project number: 2/0190/17 

duration: 1.1.2017 – 31.12.2020  

 

Research on possibilities and development of SQUID magnetometry for selected applications in biomedicine and material research 

principal investigator: Ján Maňka, Dipl. ing., PhD. 

principal investigator in INPP: Iveta Bernátová, PhD., DSc. 

project number: VEGA 2/0164/17 

duration: 1.7.2017 – 30.6.2021  

 

The aim of this research is to investigate the use of the SQUID magnetometry in study of the current problems in medicine, biology and material research. In biomedical research we will analyse the properties and magnetic characterization of the magnetic nanoparticles and nanoliquids in studies of nanoparticle traslocation into the blood vessels wall, the heart and the other organs of rats with normal and high blood pressure.

 


Past projects

Epicatechin in prevention of early development of primary hypertension: mechanisms of action in the cardiovascular and central nervous systems

Project no.: VEGA 2/0084/14

Project leader: Iveta Bernátová

Duration: 1.1.2014 – 31.12.2016

Description:

This project investigates the effect of epicatechin (Epi) in the cardiovascular and central nervous systems of normotensive, borderline hypertensive (BHR) and spontaneously hypertensive rats as well as in the young humans. Epi has been given to rats in the age of 6-7 weeks which is a critical developmental window regarding development of blood pressure. The effect of Epi on behaviour, blood pressure and selected metabolic, functional and structural parameters of the brain, heart and arteries has been determined. The attention has been paid to the mechanisms of blood pressure regulation and vascular function mediated by nitric oxide, reactive oxygen species and endothelium-derived constricting factors. In young humans Epi has been administered in flavanol-rich chocolate and the reactivity of blood pressure during mental load was determined. The results allow us to evaluate the use of Epi in prevention of hypertension in rats with genetic predisposition to hypertension as well as in humans in conditions of mental load.

 

Stress – induced pressor responses: endothelial factors vs. central regulation of sympathetic tone

Program: SAS International Collaboration

Project no.: MVTS, AV ČR 16-18

Project leader: Iveta Bernátová

Duration: 1/2016 – 12/2017
Description:
Acute stress may participate in stroke and heart attack. The mechanisms involved may be associated with inadequate acute stress-induced elevation of blood pressure (BP). The aim of this project is to reveal differences in mechanisms involved in acute stress-induced pressor responses in adult normotensive and spontaneously hypertensive (SHR) rats. We will determine the role of nitric oxide (NO) in central regulation of sympathetic tone as well as the role of endothelium-derived factors (EDFs) such as NO, superoxide and hydrogen sulfide, in modulation of stress-induced BP responses. Acute stress will be induced by air-jet to the face of the rat. The effect of particular BP regulation systems will be investigated using inhibitors specific for the given system such as pentolinium (SNS), tempol (ROS), selective inhibitors of nNOS, iNOS and eNOS and other substances to inhibit selected EDFs. Resolving differences in acute stress-induced pressor responses could provide mechanism for selective prevention of dangerous stress-induced BP increase in hypertensive subjects and thus in prevention of stress-provoked stroke and heart attack.

 

Effect of aging on the endothelial function in experimental hypertension

Funding: Slovak Society of Cardiology

Project leader: Angelika Púzserová

Duration: 17.4.2014 – 17.4.2017

Description:

The aim of this project is to investigate the impact of aging on the cardiovascular system, mainly the functional state of the endothelium in the large, medium-sized and resistance arteries during normotension and hypertension. The project studies the role of various endothelium-dependent relaxing and contracting factors in peri-pubertal, adult and senescent rats. In addition, we determine the effect of aging on deformability of red blood cells, nitric oxide bioavailability and reactive oxygen species in the heart and selected arteries.

 

Development of SQUID Gradiometric and Susceptometric Methods for Iron Homeostasis Related Bio-Applications

Project no.: VEGA 2/0152/13

Project leader: JánMaňka (Institute of Measurement Science SAS)

Project leader at INPP SAS: Iveta Bernátová

Duration: 1.1.2013 – 31.12.2016

Description:

The aim of this project is to design and optimize the SQUID gradiometric and susceptometric measuring methods and devices for detection and localization of the cancer tissue as well as for investigation of processes related to a disturbed iron metabolism in cardiovascular diseases. We investigate iron homeostasis and biomineralization in ferritin cores in the above mentioned diseases. We also investigate the limit sensitivity of this measuring system. We identify the factors which affect the diagnostic interpretation of the results achieved.

 


Collaboration

University of Buenos Aires-CONICET, School of Pharmacy and Biochemistry, Buenos Aires, Argentina

Institute of Physiology, Academy of Sciences, Prague, Czech Republic

Universidad Autonoma de Madrid, Faculty of Medicine, Madrid, Spain

University of Kragujevac, Faculty of Medicine, Kragujevac, Serbia

Experimental Research Group, Cape Peninsula University of Technology, Bellville, and Department of Physiological Sciences, University of Stellenbosch, Stellenbosch, South Africa

Institute of Heart Research SAS

Institute of Experimental Pharmacology and Toxicology SAS

Faculty of Medicine, Comenius University in Bratislava

Faculty of Electrical Engineering and Information Technology, Slovak Technical University in Bratislava