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

1994 ◽  
Vol 267 (6) ◽  
pp. H2471-H2482 ◽  
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.

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

2019 ◽  
Vol 316 (5) ◽  
pp. R563-R570 ◽  
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.

scholarly journals Salt-sensitive hypertension and cardiac hypertrophy in mice deficient in the ubiquitin ligase Nedd4-2

2008 ◽  
Vol 295 (2) ◽  
pp. F462-F470 ◽  
Author(s):  
Peijun P. Shi ◽  
Xiao R. Cao ◽  
Eileen M. Sweezer ◽  
Thomas S. Kinney ◽  
Nathan R. Williams ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Critical Role ◽  
Specific Inhibitor ◽  
Normal Diet ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Ww Domains ◽  
Salt Sensitive Hypertension

Nedd4-2 has been proposed to play a critical role in regulating epithelial Na+ channel (ENaC) activity. Biochemical and overexpression experiments suggest that Nedd4-2 binds to the PY motifs of ENaC subunits via its WW domains, ubiquitinates them, and decreases their expression on the apical membrane. Phosphorylation of Nedd4-2 (for example by Sgk1) may regulate its binding to ENaC, and thus ENaC ubiquitination. These results suggest that the interaction between Nedd4-2 and ENaC may play a crucial role in Na+ homeostasis and blood pressure (BP) regulation. To test these predictions in vivo, we generated Nedd4-2 null mice. The knockout mice had higher BP on a normal diet and a further increase in BP when on a high-salt diet. The hypertension was probably mediated by ENaC overactivity because 1) Nedd4-2 null mice had higher expression levels of all three ENaC subunits in kidney, but not of other Na+ transporters; 2) the downregulation of ENaC function in colon was impaired; and 3) NaCl-sensitive hypertension was substantially reduced in the presence of amiloride, a specific inhibitor of ENaC. Nedd4-2 null mice on a chronic high-salt diet showed cardiac hypertrophy and markedly depressed cardiac function. Overall, our results demonstrate that in vivo Nedd4-2 is a critical regulator of ENaC activity and BP. The absence of this gene is sufficient to produce salt-sensitive hypertension. This model provides an opportunity to further investigate mechanisms and consequences of this common disorder.

Daily intake of sulforaphane-rich broccoli sprouts prevents progression of high salt diet-induced gastric atrophy in H. pylori-infected C57/BL6 mice in vivo

2003 ◽  
Vol 124 (4) ◽  
pp. A5 ◽  
Author(s):  
Akinori Yanaka ◽  
Songhua Zhang ◽  
Masafumi Tauchi ◽  
Hideo Suzuki ◽  
Takeshi Shibahara ◽  
...  
Keyword(s):  
Daily Intake ◽  
Gastric Atrophy ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Broccoli Sprouts ◽  
H Pylori

Salt-sensitive hypertension develops after transient induction of ANG II-dependent hypertension in Cyp1a1-Ren2 transgenic rats

2005 ◽  
Vol 288 (4) ◽  
pp. F810-F815 ◽  
Author(s):  
Laura L. Howard ◽  
Matthew E. Patterson ◽  
John J. Mullins ◽  
Kenneth D. Mitchell
Keyword(s):  
Blood Pressure ◽  
Renal Plasma Flow ◽  
Systolic Pressure ◽  
High Salt ◽  
Ang Ii ◽  
Transgenic Rats ◽  
High Salt Diet ◽  
Blood Pressure Elevation ◽  
Salt Diet ◽  
Salt Sensitive Hypertension

Transient exposure to ANG II results in the development of salt-sensitive hypertension in rats. This study was performed to determine whether a transient hypertensive episode can induce salt-sensitive hypertension in transgenic rats with inducible expression of the mouse Ren2 renin gene [strain name TGR(Cyp1a1-Ren2)]. Systolic blood pressures were measured in conscious male Cyp1a1-Ren2 rats ( n = 6) during control conditions and during dietary administration of indole-3-carbinol (I3C; 0.15%, wt/wt), for 14 days. Systolic pressure increased from 135 ± 5 to 233 ± 7 mmHg by day 14. I3C administration was terminated and blood pressure returned to normal levels (137 ± 5 mmHg) within 10 days. Subsequently, the rats were placed on a high-salt diet (8% NaCl) for 10 days. Systolic pressure increased by 34 ± 2 mmHg throughout 10 days of the high-salt diet. Neither glomerular filtration rate nor renal plasma flow was altered in Cyp1a1-Ren2 rats with salt-sensitive hypertension. In a separate group of male Cyp1a1-Ren2 rats ( n = 6) transiently induced with 0.15% I3C for 14 days, administration of the superoxide dismutase mimetic tempol (4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl, 2 mM) attenuated the increase in systolic pressure induced by high salt. Systolic pressure increased by only 11 ± 1 mmHg throughout 8 days of a high-salt diet and tempol administration. Thus transient induction of ANG II-dependent hypertension via activation of the Cyp1a1-Ren2 transgene induces salt-sensitive hypertension in these transgenic rats. The attenuation by tempol of the high salt-induced blood pressure elevation indicates that ANG II-induced production of superoxide anion contributes to the development of salt-sensitive hypertension after transient induction of ANG II-dependent hypertension.

scholarly journals Alamandine alleviates hypertension and renal damage via oxidative-stress attenuation in Dahl rats

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Juexiao Gong ◽  
Man Luo ◽  
Yonghong Yong ◽  
Shan Zhong ◽  
Peng Li
Keyword(s):  
Oxidative Stress ◽  
Renal Dysfunction ◽  
Renal Damage ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Renal Tubular Cells ◽  
Induced Hypertension

AbstractAlamandine (Ala) is a novel member of the renin–angiotensin-system (RAS) family. The present study aimed to explore the effects of Ala on hypertension and renal damage of Dahl salt-sensitive (SS) rats high-salt diet-induced, and the mechanisms of Ala on renal-damage alleviation. Dahl rats were fed with high-salt diets to induce hypertension and renal damage in vivo, and HK-2 cells were treated with sodium chloride (NaCl) to induce renal injury in vitro. Ala administration alleviated the high-salt diet-induced hypertension, renal dysfunction, and renal fibrosis and apoptosis in Dahl SS rats. The HK-2 cells’ damage, and the increases in the levels of cleaved (c)-caspase3, c-caspase8, and c-poly(ADP-ribose) polymerase (PARP) induced by NaCl were inhibited by Ala. Ala attenuated the NaCl-induced oxidative stress in the kidney and HK-2 cells. DETC, an inhibitor of SOD, reversed the inhibitory effect of Ala on the apoptosis of HK-2 cells induced by NaCl. The NaCl-induced increase in the PKC level was suppressed by Ala in HK-2 cells. Notably, PKC overexpression reversed the moderating effects of Ala on the NaCl-induced apoptosis of HK-2 cells. These results show that Ala alleviates high-salt diet-induced hypertension and renal dysfunction. Ala attenuates the renal damage via inhibiting the PKC/reactive oxygen species (ROS) signaling pathway, thereby suppressing the apoptosis in renal tubular cells.

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

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.

Alterations in apoptosis regulatory factors during hypertrophy and heart failure

2004 ◽  
Vol 287 (1) ◽  
pp. H72-H80 ◽  
Author(s):  
Peter M. Kang ◽  
Patrick Yue ◽  
Zhilin Liu ◽  
Oleg Tarnavski ◽  
Natalya Bodyak ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Primary Cultures ◽  
High Salt ◽  
Terminal Deoxynucleotidyl Transferase ◽  
High Salt Diet ◽  
Salt Diet ◽  
Pathological Hypertrophy ◽  
Increased Sensitivity ◽  
Physiological Hypertrophy

Cardiac hypertrophy from pathological stimuli often proceeds to heart failure, whereas cardiac hypertrophy from physiological stimuli does not. In this study, physiological hypertrophy was created by a daily exercise regimen and pathological hypertrophy was created from a high-salt diet in Dahl salt-sensitive rats. The rats continued on a high-salt diet progressed to heart failure associated with an increased rate of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cardiomyocytes. We analyzed primary cultures of these hearts and found that only cardiomyocytes made hypertrophic by a pathological stimulus show increased sensitivity to apoptosis. Examination of the molecular changes associated with these distinct types of hypertrophy revealed changes in Bcl-2 family members and caspases favoring survival during physiological hypertrophy. However, in pathological hypertrophy, there were more diffuse proapoptotic changes, including changes in Fas, the Bcl-2 protein family, and caspases. Therefore, we speculate that this increased sensitivity to apoptotic stimulation along with proapoptotic changes in the apoptosis program may contribute to the development of heart failure seen in pathological cardiac hypertrophy.

scholarly journals Biocompatibility of Four Common Orthopedic Biomaterials Following a High-Salt Diet: An In Vivo Study

2017 ◽  
Vol 18 (7) ◽  
pp. 1489 ◽  
Author(s):  
Mathieu Lecocq ◽  
Cécile Bernard ◽  
Marie Felix ◽  
Jean-Marc Linares ◽  
Julien Chaves-Jacob ◽  
...  
Keyword(s):  
High Salt ◽  
In Vivo Study ◽  
High Salt Diet ◽  
Salt Diet

scholarly journals CYP2C11 played a significant role in down-regulating rat blood pressure under the challenge of a high-salt diet

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6807
Author(s):  
Wei Liu ◽  
Danjuan Sui ◽  
Huanying Ye ◽  
Zhen Ouyang ◽  
Yuan Wei
Keyword(s):  
Blood Pressure ◽  
Sodium Chloride ◽  
Normal Diet ◽  
High Salt ◽  
Sprague Dawley ◽  
Western Blots ◽  
High Salt Diet ◽  
Salt Diet ◽  
Renal Expression

Background Arachidonic acid (AA) is oxidized by cytochrome P450s (CYPs) to form epoxyeicosatrienoic acids (EETs), compounds that modulate ion transport, gene expression, and vasorelaxation. Both CYP2Cs and CYP2Js are involved in kidney EET epoxidation. Methods In this study, we used a CYP2C11-null rat model to explore the in vivo effects of CYP2C11 on vasorelaxation. For 2 months, CYP2C11-null and wild-type (WT) Sprague-Dawley rats were either fed normal lab (0.3% (w/w) sodium chloride) or high-salt (8% (w/w) sodium chloride) diets. Subsequently, an invasive method was used to determine blood pressure. Next, western blots, quantitative PCR, and immunohistochemistry were used to determine renal expression of CYPs involved in AA metabolism. Results Among CYP2C11-null rats, a high-salt diet (females: 156.79 ± 15.89 mm Hg, males: 130.25 ± 16.76 mm Hg, n = 10) resulted in significantly higher blood pressure than a normal diet (females: 118.05 ± 8.43 mm Hg, P < 0.01; males: 115.15 ± 11.45 mm Hg, P < 0.05, n = 10). Compared with WT rats under the high-salt diet, western blots showed that CYP2C11-null rats had higher renal expression of CYP2J2 and CYP4A. This was consistent with the results of immunohistochemistry and the qPCR, respectively. The two rat strains did not differ in the renal expression of CYP2C23 or CYP2C24. Conclusion Our findings suggested that CYP2C11 plays an important role in lowering blood pressure under the challenge of a high-salt diet.

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