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Article

Deleterious Effects of Hyperactivity of the Renin-Angiotensin System and Hypertension on the Course of Chemotherapy-Induced Heart Failure after Doxorubicin Administration: A Study in Ren-2 Transgenic Rat

1
Department of Cardiology, University Hospital Motol and 2nd Faculty of Medicine, Charles University, 150 06 Prague, Czech Republic
2
Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic
3
Department of Cardiology, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic
4
Department of Renal and Body Fluid Physiology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 01-224 Warsaw, Poland
5
Department of Pathophysiology, 2nd Faculty of Medicine, Charles University, 110 00 Prague, Czech Republic
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(24), 9337; https://doi.org/10.3390/ijms21249337
Received: 21 November 2020 / Revised: 3 December 2020 / Accepted: 4 December 2020 / Published: 8 December 2020
Doxorubicin’s (DOX) cardiotoxicity contributes to the development of chemotherapy-induced heart failure (HF) and new treatment strategies are in high demand. The aim of the present study was to characterize a DOX-induced model of HF in Ren-2 transgenic rats (TGR), those characterized by hypertension and hyperactivity of the renin-angiotensin-aldosterone system, and to compare the results with normotensive transgene-negative, Hannover Sprague-Dawley (HanSD) rats. DOX was administered for two weeks in a cumulative dose of 15 mg/kg. In HanSD rats DOX administration resulted in the development of an early phase of HF with the dominant symptom of bilateral cardiac atrophy demonstrable two weeks after the last DOX injection. In TGR, DOX caused substantial impairment of systolic function already at the end of the treatment, with further progression observed throughout the experiment. Additionally, two weeks after the termination of DOX treatment, TGR exhibited signs of HF characteristic for the transition stage between the compensated and decompensated phases of HF. In conclusion, we suggest that DOX-induced HF in TGR is a suitable model to study the pathophysiological aspects of chemotherapy-induced HF and to evaluate novel therapeutic strategies to combat this form of HF, which are urgently needed. View Full-Text
Keywords: chemotherapy-induced heart failure; doxorubicin; hypertension; renin-angiotensin-aldosterone system chemotherapy-induced heart failure; doxorubicin; hypertension; renin-angiotensin-aldosterone system
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MDPI and ACS Style

Kala, P.; Bartušková, H.; Piťha, J.; Vaňourková, Z.; Kikerlová, S.; Jíchová, Š.; Melenovský, V.; Hošková, L.; Veselka, J.; Kompanowska-Jezierska, E.; Sadowski, J.; Gawrys, O.; Maxová, H.; Červenka, L. Deleterious Effects of Hyperactivity of the Renin-Angiotensin System and Hypertension on the Course of Chemotherapy-Induced Heart Failure after Doxorubicin Administration: A Study in Ren-2 Transgenic Rat. Int. J. Mol. Sci. 2020, 21, 9337. https://doi.org/10.3390/ijms21249337

AMA Style

Kala P, Bartušková H, Piťha J, Vaňourková Z, Kikerlová S, Jíchová Š, Melenovský V, Hošková L, Veselka J, Kompanowska-Jezierska E, Sadowski J, Gawrys O, Maxová H, Červenka L. Deleterious Effects of Hyperactivity of the Renin-Angiotensin System and Hypertension on the Course of Chemotherapy-Induced Heart Failure after Doxorubicin Administration: A Study in Ren-2 Transgenic Rat. International Journal of Molecular Sciences. 2020; 21(24):9337. https://doi.org/10.3390/ijms21249337

Chicago/Turabian Style

Kala, Petr, Hana Bartušková, Jan Piťha, Zdenka Vaňourková, Soňa Kikerlová, Šárka Jíchová, Vojtěch Melenovský, Lenka Hošková, Josef Veselka, Elzbieta Kompanowska-Jezierska, Janusz Sadowski, Olga Gawrys, Hana Maxová, and Luděk Červenka. 2020. "Deleterious Effects of Hyperactivity of the Renin-Angiotensin System and Hypertension on the Course of Chemotherapy-Induced Heart Failure after Doxorubicin Administration: A Study in Ren-2 Transgenic Rat" International Journal of Molecular Sciences 21, no. 24: 9337. https://doi.org/10.3390/ijms21249337

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