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

Autor: Olga Gawrys, Elzbieta Kompanowska-Jezierska, Hana Bartušková, Petr Kala, Zdenka Vaňourková, Lenka Hošková, Vojtěch Melenovský, Jan Piťha, H. Maxová, Soňa Kikerlová, Josef Veselka, Šárka Jíchová, Luděk Červenka, Janusz Sadowski
Rok vydání: 2020
Předmět:
hypertension
Transgene
Antineoplastic Agents
Blood Pressure
030204 cardiovascular system & hematology
Pharmacology
doxorubicin
Article
Catalysis
Rats
Sprague-Dawley
Renin-Angiotensin System
lcsh:Chemistry
Inorganic Chemistry
03 medical and health sciences
0302 clinical medicine
Atrophy
Renin
Renin–angiotensin system
polycyclic compounds
medicine
Animals
Doxorubicin
Physical and Theoretical Chemistry
lcsh:QH301-705.5
Molecular Biology
Spectroscopy
Heart Failure
Cardiotoxicity
Cumulative dose
business.industry
Organic Chemistry
chemotherapy-induced heart failure
General Medicine
medicine.disease
Pathophysiology
Rats
Computer Science Applications
carbohydrates (lipids)
renin-angiotensin-aldosterone system
lcsh:Biology (General)
lcsh:QD1-999
030220 oncology & carcinogenesis
Heart failure
Female
business
medicine.drug
Zdroj: International Journal of Molecular Sciences, Vol 21, Iss 9337, p 9337 (2020)
International Journal of Molecular Sciences
Volume 21
Issue 24
ISSN: 1422-0067
DOI: 10.3390/ijms21249337
Popis: Doxorubicin&rsquo
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.
Databáze: OpenAIRE
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