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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.

Author information

1
Department of medical cellbiology, Uppsala University, Sweden.
2
Department of Biomedicine, University of Bergen, Norway.
3
Department of Biomedicine, Institute of Medicine, University of Bergen.
4
Galderma Nordic AB, Galderma Nordic AB, Sweden.
5
Renal research group, Institute of Medicine, University of Bergen.
6
Biomedicine, University of Bergen, Norway.
7
Department of medical cellbiology, Uppsala Universitet, Sweden.

Abstract

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.

KEYWORDS:

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

PMID:
30840486
DOI:
10.1152/ajpregu.00373.2018

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