Medical University of Bialystok. Research & Science.
  • 25.03.2024 Zakład Fizjologii i Patofizjologii Doświadczalnej

    Research & Science

     Grants

    • Cannabidiol as a potential cardioprotective agent in isolated rat atrium under hypoxic conditions (MINIATURA; 2019 – 2020, principal investigator A. Pędzińska-Betiuk,)

    • The comprehensive evaluation of potentially protective action of cannabidiol in the experimental model of pulmonary arterial hypertension (PRELUDIUM, 2018-2020; principal investigator: Olga Karpińska; research supervisor: dr Hanna Kozłowska)

    • The influence of simultaneous inhibition of endocannabinoid degrading enzymes FAAH and MAGL by JZL195 on the cardiovascular system, oxidative stress and inflammation in spontaneously hypertensive and normotensive rats. (PRELUDIUM, 2017-2019; principal investigator: Marek Toczek; research supervisor: Prof. Barbara Malinowska)
    • Complex effects of cannabidiol on the cardiovascular system, oxidative stress and heart metabolism in experimental models of hypertension (OPUS, 2016 – 2019; principal investigator: Prof. Barbara Malinowska)
    • Role of endocannabinoids in the regulation of the cardiovascular system, oxidative stress and heart metabolism in the models of primary and secondary hypertension (OPUS, 2012 – 2016; principal investigator: Prof. Barbara Malinowska)

     

    Scope of scientific activity

     
    • role of exogenous and endogenous cannabinoids in regulation of cardiovascular system in physiological and pathophysiological conditions
    • functions of the low-affinity β1-adreno-receptors in regulation of cardiovascular system in rats
    • involvement of the selected presynaptic receptors in central nervous system in regulation of cardiovascular system

     

    Rat models

     
    • hypertension, myocardial ischemia, cardiogenic and septic shock, diabetes

     

    Experimental techniques

    In vitro methods:

    • evaluation of mechanistic responses (isometric conctraction) of isolated blood vessels of the rat (mesenteric, renal and pulmonary arteries and aorta) and human (lung artery) (PhD H. Kozłowska, PhD M. Baranowska-Kuczko, MSc M. Kloza)
    • evaluation of isolated rat heart responses in the Langendorff system (PhD A. Pędzińska-Betiuk, MSc J. Weresa)
    • evaluation of responses of the isolated rat atria and the right atrial appendage (PhD A. Pędzińska-Betiuk, PhD B. Gajo, MSc J. Weresa)

    In vivo methods:

    • evaluation of cardivascular responses in anaesthetized and pithed rat model (heart rate, blood pressure, left ventricular pressure, mesenteric and renal blood flow) (MSc M. Toczek)
    • investigation of the function of peripheral pre- and postsynaptic receptors in the rat cardiovascular system (the electrical stimulation of preganglionic sympathetic nerve fibers innervating the heart and resistance vessels and electrical stimulation of the vagus nerve in the pithed rat, von Bezold-Jarisch reflex) (MSc M. Toczek, MSc R. Kossakowski)
    • stereotaxic microinjections into the paraventricular nucleus (PVN) (MSc eng. K. Mińczuk)

     

    Publications

    • Harasim-Symbor E., Polak A., Pędzińska-Betiuk A., Weresa J., Malinowska B., Lewandowska A., Kasacka I., Chabowski A. Fatty acid amide hydrolase inhibitor (URB597) as a regulator of myocardial lipid metabolism in spontaneously hypertensive rats. Chem Phys Lipids. 2019; 218:141-148.
    • Weresa J., Pędzińska-Betiuk A., Kossakowski R., Malinowska B. Cannabinoid CB1 and CB2 receptors antagonists AM251 and AM630 differentially modulate the chronotropic and inotropic effects of isoprenaline in isolated rat atria. Pharmacol Rep. 2019; 71:82-89.
    • Malinowska B., Toczek M., Pędzińska-Betiuk A., Schlicker E. Cannabinoids in arterial, pulmonary and portal hypertension - mechanisms of action and potential therapeutic significance. Br J Pharmacol. 2019; 176:1395-1411.
    • Kossakowski R., Schlicker E., Toczek M., Weresa J., Malinowska B. Cannabidiol Affects the Bezold-Jarisch Reflex via TRPV1 and 5-HT3 Receptors and Has Peripheral Sympathomimetic Effects in Spontaneously Hypertensive and Normotensive Rats. Front Pharmacol. 2019;10:500.
    • Gromotowicz-Poplawska A., Kloza M., Aleksiejczuk M., Marcinczyk N., Szemraj J., Kozłowska H., Chabielska E. Nitric oxide as a modulator in platelet- and endothelium-dependent antithrombotic effect of eplerenone in diabetic rats. J Physiol Pharmacol. 2019; 70(2).
    • Kloza M., Baranowska-Kuczko M., Toczek M., Kusaczuk M., Sadowska O., Kasacka I., Kozłowska H. Modulation of Cardiovascular Function in Primary Hypertension in Rat by SKA-31, an Activator of KCa2.x and KCa3.1 Channels. Int J Mol Sci. 2019; 20(17).
    • Biernacki M., Malinowska B., Timoszuk M., Toczek M., Jastrząb A., Remiszewski P., Skrzydlewska E. Hypertension and chronic inhibition of endocannabinoid degradation modify the endocannabinoid system and redox balance in rat heart and plasma. Prostaglandins Other Lipid Mediat. 2018; 138:54-63.
    • Polak A., Harasim-Symbor E., Malinowska B., Kasacka I., Lewandowska A., Chabowski A. The Endocannabinoid System Affects Myocardial Glucose Metabolism in the DOCA-Salt Model of Hypertension. Cell Physiol Biochem. 2018; 46:727-739.
    • Toczek M., Malinowska B. Enhanced endocannabinoid tone as a potential target of pharmacotherapy. Life Sci. 2018; 204:20-45.
    • Biernacki M., Łuczaj W., Jarocka-Karpowicz I., Ambrożewicz E., Toczek M., Skrzydlewska E. The Effect of Long-Term Administration of Fatty Acid Amide Hydrolase Inhibitor URB597 on Oxidative Metabolism in the Heart of Rats with Primary and Secondary Hypertension. Molecules. 2018; ;23(9).
    • Biernacki M., Ambrożewicz E., Gęgotek A., Toczek M., Skrzydlewska E. Long-term administration of fatty acid amide hydrolase inhibitor (URB597) to rats with spontaneous hypertension disturbs liver redox balance and phospholipid metabolism. Adv Med Sci. 2019; 64:15-23.
    • Biernacki M, Ambrożewicz E, Gęgotek A, Toczek M, Bielawska K, Skrzydlewska E. Redox system and phospholipid metabolism in the kidney of hypertensive rats after FAAH inhibitor URB597 administration. Redox Biol. 2018; 15:41-50.
    • Karpińska O., Baranowska-Kuczko M., Malinowska B., Kloza M., Kusaczuk M., Gęgotek A., Golec P., Kasacka I., Kozłowska H. Mechanisms of l-alpha-lysophosphatidylinositol-induced relaxation in human pulmonary arteries. Life Sci. 2018;192:38-45.
    • Karpińska O., Baranowska-Kuczko M., Kloza M., Kozłowska H. Endocannabinoids modulate Gq/11 protein-coupled receptor agonist-induced vasoconstriction via a negative feedback mechanism. J Pharm Pharmacol. 2018;70:214-222.
    • Kloza M., Baranowska-Kuczko M., Malinowska B., Karpińska O., Harasim-Symbor E., Kasacka I., Kozłowska H. The influence of DOCA-salt hypertension and chronic administration of the FAAH inhibitor URB597 on KCa2.3/KCa3.1-EDH-type relaxation in rat small mesenteric arteries.  Vascul Pharmacol. 2017;99:65-73.
    • Polak A., Harasim-Symbor E., Malinowska B., Kasacka I., Pędzińska-Betiuk A., Weresa J., Chabowski A. The effects of chronic FAAH inhibition on myocardial lipid metabolism in normotensive and DOCA-salt hypertensive rats. Life Sci. 2017;183:1-10.

    • Pedzinska-Betiuk A., Weresa J., Toczek M., Baranowska-Kuczko M., Kasacka I., Harasim-Symbor E., Malinowska B. Chronic inhibition of fatty acid amide hydrolase by URB597 produces differential effects on cardiac performance in normotensive and hypertensive rats. Br J Pharmacol. 2017;174:2114-2129.

    • Karpińska O., Baranowska-Kuczko M., Kloza M., Ambrożewicz E., Kozłowski T., Kasacka .I, Malinowska B., Kozłowska H. Activation of CB1 receptors by 2-arachidonoylglycerol attenuates vasoconstriction induced by U46619 and angiotensin II in human and rat pulmonary arteries. Am J Physiol Regul Integr Comp Physiol. 2017;312:R883-R893.

    • Grzęda E., Schlicker E., Toczek M., Zalewska I., Baranowska-Kuczko M., Malinowska B.: CB1 receptor activation in the rat paraventricular nucleus induces bi-directional cardiovascular effects via modification of glutamatergic and GABAergic neurotransmission. Naunyn Schmiedebergs Arch Pharmacol. 2017;390:25-35
    • Tokajuk A., Karpińska O., Zakrzeska A, Bienias K, Prokopiuk S., Kozłowska H., Kasacka I., Chabielska E., Car H. Dysfunction of aorta is prevented by whey protein concentrate-80 in venous thrombosis-induced rats. Journal of Functional Foods. 2016; 27: 365-375
    • Toczek M., Baranowska-Kuczko M., Grzęda E., Pędzińska-Betiuk A., Weresa J., Malinowska B.: Age-specific influences of chronic administration of the fatty acid amide hydrolase inhibitor URB597 on cardiovascular parameters and organ hypertrophy in DOCA-salt hypertensive rats. Pharmacol Rep. 2016;68:363-9.
    • Biernacki M., Łuczaj W., Gęgotek A., Toczek M., Bielawska K., Skrzydlewska E.: Crosstalk between liver antioxidant and the endocannabinoid systems after chronic administration of the FAAH inhibitor, URB597, to hypertensive rats. Toxicol Appl Pharmacol. 2016;301:31-41.
    • Baranowska-Kuczko M., Kozłowska H., Kloza M., Karpińska O., Toczek M., Harasim E., Kasacka .I, Malinowska B.: Protective role of cannabinoid CB1 receptors and vascular effects of chronic administration of FAAH inhibitor URB597 in DOCA-salt hypertensive rats. Life Sci. 2016;151:288-99.
    • Grzeda E., Schlicker E., Luczaj W., Harasim E., Baranowska-Kuczko M., Malinowska B.: Bi-directional CB1 receptor-mediated cardiovascular effects of cannabinoids in anaesthetized rats: role of the paraventricular nucleus. J Physiol Pharmacol. 2015;66:343-53.
    • Toczek M., Schlicker E., Grzęda E., Malinowska B.: Enhanced function of inhibitory presynaptic cannabinoid CB1 receptors on sympathetic nerves of DOCA-salt hypertensive rats. Life Sci. 2015;138:78-85.
    • Karabowicz P., Schlicker E., Pędzińska-Betiuk A., Kloza M., Malinowska B.: The adrenal medulla, not CB1 receptors, mediates the inhibitory effect of acute transverse aortic constriction on the neurogenic vasopressor response. Life Sci. 2015;138:86-93.
    • Baranowska-Kuczko M., Kozłowska H., Kozłowski M., Schlicker E., Kloza M., Surażyński A., Grzęda E., Malinowska B.: Mechanisms of endothelium-dependent relaxation evoked by anandamide in isolated human pulmonary arteries. Naunyn Schmiedebergs Arch Pharmacol. 2014;387:477-86.
    • Schlicker E., Pędzińska-Betiuk A., Kozłowska H., Szkaradek N., Żelaszczyk D., Baranowska-Kuczko M., Kieć-Kononowicz K., Marona H., Malinowska B.: MH-3: evidence for non-competitive antagonism towards the low-affinity site of β1-adrenoceptors. Naunyn Schmiedebergs Arch Pharmacol. 2014;387:743-52.
    • Kloza M., Baranowska-Kuczko M., Pędzińska-Betiuk A., Jackowski K., Kozłowska H.: Teoria serotoninowa a tętnicze nadciśnienie płucne. Postepy Hig Med Dosw. 2014;68:738-48.
    • Karabowicz P., Grzęda E., Baranowska-Kuczko M., Malinowska B.: Znaczenie endokannabinoidu 2-arachidonyloglicerolu w fizjologii i patofizjologii układu krążenia. Postepy Hig Med Dosw. 2014;68:814-27.
    • Ilayan E., Feliszek M., Malinowska B., Schlicker E.: Do cannabinoids exhibit a tyramine-like effect? Naunyn Schmiedebergs Arch Pharmacol. 2013;386:1041-6.
    • Kozłowska H., Baranowska-Kuczko M., Schlicker E., Kozłowski M., Kloza M., Malinowska B.: Relaxation of human pulmonary arteries by PPARγ agonists. Naunyn Schmiedebergs Arch Pharmacol. 2013;386:445-53.
    • Rudź R., Schlicker E., Baranowska U., Marciniak J., Karabowicz P., Malinowska B.: Acute myocardial infarction inhibits the neurogenic tachycardic and vasopressor response in rats via presynaptic cannabinoid type 1 receptor. J Pharmacol Exp Ther. 2012;343:198-205.
    • Baranowska-Kuczko M., MacLean MR., Kozłowska H., Malinowska B.: Endothelium-dependent mechanisms of the vasodilatory effect of the endocannabinoid, anandamide, in the rat pulmonary artery. Pharmacol Res. 2012;66:251-9.
    • Kozłowska H., Baranowska-Kuczko M., Schlicker E., Kozłowski M., Zakrzeska A., Grzęda E., Malinowska B.: EP₃ receptor-mediated contraction of human pulmonary arteries and inhibition of neurogenic tachycardia in pithed rats. Pharmacol Rep. 2012;64:1526-36.
    • Malinowska B, Baranowska-Kuczko M, Schlicker E. Triphasic blood pressure responses to cannabinoids: do we understand the mechanism? Br J Pharmacol. 2012;165:2073-88.
    • Lupiński SŁ., Schlicker E., Pędzińska-Betiuk A., Malinowska B.: Acute myocardial ischemia enhances the vanilloid TRPV1 and serotonin 5-HT3 receptor-mediated Bezold-Jarisch reflex in rats. Pharmacol Rep. 2011;63:1450-9.
    • Zakrzeska A., Schlicker E., Baranowska M., Kozłowska H., Kwolek G., Malinowska B.: A cannabinoid receptor, sensitive to O-1918, is involved in the delayed hypotension induced by anandamide in anaesthetized rats. Br J Pharmacol. 2010;160:574-84.
    • Malinowska B., Zakrzeska A., Kurz CM., Göthert M., Kwolek G., Wielgat P., Braszko JJ., Schlicker E.: Involvement of central beta2-adrenergic, NMDA and thromboxane A2 receptors in the pressor effect of anandamide in rats. Naunyn Schmiedebergs Arch Pharmacol. 2010;381:349-60.
    • Günther J., Schulte K., Wenzel D., Malinowska B., Schlicker E.: Prostaglandins of the E series inhibit monoamine release via EP3 receptors: proof with the competitive EP3 receptor antagonist L-826,266. Naunyn Schmiedebergs Arch Pharmacol. 2010;381:21-31.
    • Zelaszczyk D., Kozlowska H., Baranowska U., Baranowska M., Reutelsterz A., Kiec-Kononowicz K., Malinowska B., Schlicker E.: Four close bupranolol analogues are antagonists at the low-affinity state of beta1-adrenoceptors. J Physiol Pharmacol. 2009;60:51-60.
    • Lupiński SŁ., Schlicker E., Pędzińska-Betiuk A., Malinowska B.: Odruch Bezolda-Jarischa w niedokrwieniu mięśnia sercowego. Pharmacol Rep. 2011;63:1450-9.
    • Kurz C., Baranowska U., Lupiński S., Göthert M., Malinowska B., Schlicker E.: Urethane, but not pentobarbitone, attenuates presynaptic receptor function in rats: a contribution to the choice of anaesthetic. Br J Pharmacol. 2009;157:1474-82.
    • Baranowska U., Göthert M., Rudz R., Malinowska B.: Methanandamide allosterically inhibits in vivo the function of peripheral nicotinic acetylcholine receptors containing the alpha 7-subunit. J Pharmacol Exp Ther. 2008;326:912-9.
    • Malinowska B., Lupinski S., Godlewski G., Baranowska U., Schlicker E.: Role of endocannabinoids in cardiovascular shock. J Physiol Pharmacol. 2008;59 Suppl 8:91-107.
    • Kozłowska H., Baranowska M., Schlicker E., Kozłowski M., Laudański J., Malinowska B.: Virodhamine relaxes the human pulmonary artery through the endothelial cannabinoid receptor and indirectly through a COX product. Br J Pharmacol. 2008;155:1034-42.
    • Rudź R., Baranowska U., Malinowska B.: Znaczenie kannabinoidów w niewydolności serca. Postepy Hig Med Dosw. 2008;62:174-84.
    • Kozłowska H., Baranowska M., Gromotowicz A., Malinowska B.: EDHF - śródbłonkowy czynnik hiperpolaryzujący. Znaczenie w fizjologii i chorobach naczyń krwionośnych. Postepy Hig Med Dosw. 2007;61:555-64.
    • Kozłowska H., Baranowska M., Schlicker E., Kozłowski M., Laudański J., Malinowska B.: Identification of the vasodilatory endothelial cannabinoid receptor in the human pulmonary artery. J Hypertens. 2007;25:2240-8.
    • Baranowska M., Kozłowska H., Korbut A., Malinowska B.: Kanały potasowe w naczyniach krwionośnych ich znaczenie w fizjologii i patologii. Postepy Hig Med Dosw. 2007;61:596-605.
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