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Am J Physiol Regul Integr Comp Physiol. 2019 Mar 6. doi: 10.1152/ajpregu.00373.2018. [Epub ahead of print]

Time-course of decompensation after angiotensin II and high-salt diet in Balb/CJ mice suggests pulmonary hypertension-induced cardiorenal syndrome.

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Department of medical cellbiology, Uppsala University, Sweden.
Department of Biomedicine, University of Bergen, Norway.
Department of Biomedicine, Institute of Medicine, University of Bergen.
Galderma Nordic AB, Galderma Nordic AB, Sweden.
Renal research group, Institute of Medicine, University of Bergen.
Biomedicine, University of Bergen, Norway.
Department of medical cellbiology, Uppsala Universitet, Sweden.


Genetic background of a mouse strain determines its susceptibility to disease. C57BL/6J and Balb/CJ are two widely used inbred mouse strains that we found react dramatically differently to angiotensin II and high-salt diet (AngII+Salt). Balb/CJ show increased mortality associated with anuria and edema formation while C57BL/6J develop arterial hypertension but do not decompensate and die. Clinical symptoms of heart failure in Balb/CJ mice gave the hypothesis that AngII+Salt impairs cardiac function and induces cardiac remodelling in male Balb/CJ, but not in male C57BL/6J mice. To test this hypothesis, we measured cardiac function using echocardiography, before treatment and every day for seven days during treatment with AngII+Salt. Interestingly, pulsed wave Doppler of pulmonary artery flow indicated increased pulmonary vascular resistance and right ventricle systolic pressure in Balb/CJ mice, already 24 hours after starting AngII+Salt treatment. In addition, Balb/CJ mice showed abnormal diastolic filling indicated by reduced early and late filling and increased isovolumic relaxation time. Further, Balb/CJ exhibited lower cardiac output compared to C57BL/6J even though they retained more sodium and water, as assessed using metabolic cages. Left posterior wall thickness increased during AngII+Salt treatment but did not differ between the strains. In conclusion, AngII+Salt treatment causes early restriction of pulmonary flow, reduced left ventricular filling and cardiac output in Balb/CJ, which results in fluid retention and peripheral edema. This makes Balb/CJ a potential model to study the adaptive capacity of the heart for identifying new disease mechanisms and drug targets.


animal model; congestive heart failure; pulmonary hypertension; right-sided heart failure


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