BALB/cJBom Treated with Angiotensin II and High Salt Diet Develop Pulmonary Hypertension and Right Sided Heart Failure while C57BL/6J Mice do not

Genetic background of different mouse strains determines their susceptibility to disease. We have previously shown that Balb/CJ and C57BL/6J mice develop cardiac hypertrophy to the same degree when treated with a combination of angiotensin II and high-salt diet (ANG II+Salt), but only Balb/CJ show impaired cardiac function associated with edema development and substantial mortality. We hypothesized that the different response to ANG II+Salt is due to the different genetic backgrounds of Balb/CJ and C57BL/6J. To address this we performed quantitative trait locus (QTL) mapping of second filial generation (F2) of mice derived from a backcross between Balb/CJ and first filial generation (F1) of mice. Cardiac function was measured with echocardiography, glomerular filtration rate using FITC-inulin clearance, fluid and electrolyte balance in metabolic cages, and blood pressure with tail-cuff at baseline and on the fourth day of treatment with ANG II+Salt. A total of nine QTLs were found to be linked to different phenotypes in ANG II+Salt-treated F2 mice. A QTL on chromosome 3 was linked to cardiac output, and a QTL on chromosome 12 was linked to isovolumic relaxation time. QTLs on chromosome 2 and 3 were linked to urine excretion and sodium excretion. Eight genes located at the different QTLs contained coding nonsynonymous SNPs published in the mouse genome database that differ between Balb/CJ and C57BL/6J. In conclusion, ANG II+Salt-induced acute decompensation in Balb/CJ is genetically linked to several QTLs, indicating a multifaceted phenotype. The present study identified potential candidate genes that may represent important pathways in acute decompensated heart failure.

Download Full-text

Transition from compensatory hypertrophy to dilated, failing left ventricles in Dahl salt-sensitive rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1994.267.6.h2471 ◽

1994 ◽

Vol 267 (6) ◽

pp. H2471-H2482 ◽

Cited By ~ 26

Author(s):

M. Inoko ◽

Y. Kihara ◽

I. Morii ◽

H. Fujiwara ◽

S. Sasayama

Keyword(s):

Heart Failure ◽

Systolic Pressure ◽

Myocardial Necrosis ◽

Compensatory Hypertrophy ◽

High Salt ◽

High Salt Diet ◽

Tension Development ◽

Salt Diet ◽

The Right

To establish an experimental model for studying a specific transitional stage for compensatory hypertrophy to heart failure, we studied the pathophysiology of the left ventricle (LV) in Dahl salt-sensitive (DS) rats fed a high-salt diet. DS rats fed an 8% NaCl diet after the age of 6 wk developed concentric LV hypertrophy at 11 wk, followed by marked LV dilatation at 15-20 wk. During the latter stage, the DS rats showed labored respiration with LV global hypokinesis. All the DS rats died within 1 wk by massive pulmonary congestion. The dissected left ventricles revealed chamber dilatation and a marked increase in mass without myocardial necrosis. In contrast, corresponding Dahl salt-resistant (DR) rats fed the same diet showed neither mortality nor any of these pathological changes. The in vivo LV end-systolic pressure-volume relationship shifted to the right with a less steep slope in the failing DS rats compared with that in age-matched DR rats. Isometric contractions of LV papillary muscles isolated from these DS rats showed reduced tension development in the failing stage, but normal tension development in the hypertrophied stage. In conclusion, the DS rat fed a high-salt diet is a useful model showing rapidly developing congestive heart failure, in which the transition from compensatory hypertrophy to decompensatory dilatation of LV is easily and consistently manifested.

Download Full-text

Hypertension in Dahl salt-sensitive rats: biochemical and immunohistochemical studies

Clinical Science ◽

10.1042/cs0830013 ◽

1992 ◽

Vol 83 (1) ◽

pp. 13-22 ◽

Cited By ~ 33

Author(s):

J. Bouhnik ◽

J. P. Richoux ◽

H. Huang ◽

F. Savoie ◽

T. Baussant ◽

...

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Plasma Renin Activity ◽

Plasma Renin ◽

High Salt ◽

Renin Activity ◽

Deficient Diet ◽

High Salt Diet ◽

Salt Diet ◽

Plasma Angiotensin

1. The renin-angiotensin and kinin-kallikrein systems of Dahl salt-sensitive and salt-resistant rats fed diets with different salt contents were analysed using biochemical and immunocytochemical techniques. 2. Blood pressure increased by 45% in salt-sensitive rats only, after 4 weeks on a high-salt diet. The plasma renin activity and plasma angiotensin II concentration remained at the same levels in salt-sensitive rats on the high-salt diet as on the normal salt diet, whereas the plasma renin activity and plasma angiotensin II concentration of salt-resistant rats fed the high-salt diet were lower. The plasma renin activity and the plasma angiotensin II concentration were elevated in both salt-resistant and salt-sensitive rats fed the salt-deficient diet but were much more elevated in salt-resistant than in salt-sensitive rats. 3. The kidney immunocytochemical data paralleled the data on plasma parameters. Salt-sensitive rats had fewer renin positive juxtaglomerular apparatuses than salt-resistant rats on the normal diet, and the increase on the sodium-deficient diet was also smaller in salt-sensitive rats. Salt-sensitive rats fed the high-salt diet and the standard diet had almost no angiotensin II immunoreactivity compared with the salt-resistant rats on the same diets. 4. The total renal kallikrein content of salt-sensitive rats was lower than that of salt-resistant rats on all three diets, as was the amount of kallikrein excreted in the urine on the standard and the high-salt diets. The differences resulted from a reduction in active kallikrein. The increase in kallikrein in salt-sensitive and salt-resistant rats on the salt-deficient diet was not significantly different. 5. There were similar changes in immunopositive kallikrein in the kidneys of salt-sensitive and salt-resistant rats with diet, with a large increase in kallikrein biosynthesis on the low-salt diet. The plasma concentration of high-molecular-mass kininogen was not significantly different in salt-sensitive and salt-resistant rats, but there was a significant increase in T-kininogen in salt-sensitive rats fed the high-salt diet. 6. In conclusion, the absence of decreases in the plasma renin activity and the plasma angiotensin II concentration in salt-sensitive rats fed the high-salt diet might partially explain the increase in blood pressure.

Download Full-text

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00373.2018 ◽

2019 ◽

Vol 316 (5) ◽

pp. R563-R570 ◽

Cited By ~ 3

Author(s):

Mediha Becirovic-Agic ◽

Sofia Jönsson ◽

Maria K. Tveitarås ◽

Trude Skogstrand ◽

Tine V. Karlsen ◽

...

Keyword(s):

Cardiac Output ◽

Angiotensin Ii ◽

Cardiac Function ◽

Systolic Pressure ◽

Left Ventricular ◽

High Salt ◽

Ang Ii ◽

Salt Treatment ◽

High Salt Diet ◽

Salt Diet

The 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 (ANG II + 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 ANG II + Salt impairs cardiac function and induces cardiac remodeling 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 7 days during treatment with ANG II + 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 h after ANG II + Salt treatment was started. In addition, Balb/CJ mice showed abnormal diastolic filling indicated by reduced early and late filling and increased isovolumic relaxation time. Furthermore, Balb/CJ exhibited lower cardiac output compared with C57BL/6J even though they retained more sodium and water, as assessed using metabolic cages. Left posterior wall thickness increased during ANG II + Salt treatment but did not differ between the strains. In conclusion, ANG II + Salt treatment causes early restriction of pulmonary flow and 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.

Download Full-text

Deletion of protein kinase B2 preserves cardiac function by blocking interleukin-6-mediated injury and restores blood pressure during angiotensin II/high-salt-diet-induced hypertension

Journal of Hypertension ◽

10.1097/hjh.0000000000001613 ◽

2018 ◽

Vol 36 (4) ◽

pp. 834-846 ◽

Cited By ~ 4

Author(s):

Shuai Yang ◽

Dandan Chen ◽

Fan Chen ◽

Xinmei Zhao ◽

Yubin Zhang ◽

...

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Protein Kinase ◽

Cardiac Function ◽

Interleukin 6 ◽

High Salt ◽

High Salt Diet ◽

Salt Diet ◽

Induced Hypertension

Download Full-text

Celiac ganglionectomy abolishes the chronic vasoconstrictor responses to angiotensin II (AngII) in conscious rats consuming a high salt diet

The FASEB Journal ◽

10.1096/fasebj.21.6.a1219 ◽

2007 ◽

Vol 21 (6) ◽

Author(s):

John W. Osborn ◽

Pilar Guzman ◽

Andrew King ◽

Gregory Fink

Keyword(s):

Angiotensin Ii ◽

High Salt ◽

High Salt Diet ◽

Salt Diet ◽

Conscious Rats ◽

Celiac Ganglionectomy

Download Full-text

Early Passive Leg Movement Prevents Against the Development of Heart Failure With Preserved Ejection Fraction in Rats

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.655009 ◽

2021 ◽

Vol 8 ◽

Author(s):

Jian Liu ◽

Xi-xin Ji ◽

Yang Fu ◽

Wen-chao Zhang ◽

Hui-fang Ji ◽

...

Keyword(s):

Heart Failure ◽

Blood Vessel ◽

Signaling Pathway ◽

High Salt ◽

Preserved Ejection Fraction ◽

High Salt Diet ◽

Salt Diet ◽

Leg Movement ◽

Early Passive ◽

Tgf Β1

Exercising was reported by several studies to bring great benefits to heart failure with preserved ejection fraction (HFpEF), which reduced the hospitalization and the mortality of heart failure. However, the underlying mechanism of exercising on HFpEF remains unclear. In the present study, we designed and constructed a device that can perform early passive leg movement (ePLM) in rats and further observed whether treatment of ePLM exerts protective effects on HFpEF of rats. Rats were fed with high salt feed to establish an animal model of pre-clinical diastolic dysfunction (PDD), which would eventually develop into HFpEF, and then treated rats with ePLM. We conducted several experiments to evaluate the conditions of heart and blood vessel. The results show that diastolic functions of heart and blood vessel in rats were significantly improved by treatment of ePLM. We also found that pathological injuries of heart and blood vessel were ameliorated after treatment of ePLM. Moreover, treatment of ePLM decreased the protein levels of Collagen type I, Collagen type III, MMP2, and MMP9 in heart and blood vessel, indicating that cardiac and vascular fibrosis were reduced apparently by treatment of ePLM. Further investigation suggested that treatment of ePLM probably inhibit the activation of TGF-β1/Smad3 signaling pathway as well as promote the activation of Akt/eNOS signaling pathway in high salt diet induced HFpEF. In conclusion, treatment of ePLM alleviated high salt diet induced HFpEF by inhibiting fibrosis via suppressing TGF-β1/Smad3 signaling pathway as well as activating Akt/eNOS signaling pathway, implicating treatment of ePLM as a promising novel non-pharmacological approach for HFpEF.

Download Full-text