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 Quantitative trait loci associated with angiotensin II and high-salt diet induced acute decompensated heart failure in Balb/CJ mice

2019 ◽  
Vol 51 (7) ◽  
pp. 279-289
Author(s):  
Mediha Becirovic-Agic ◽  
Sofia Jönsson ◽  
Michael Hultström
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Cardiac Function ◽  
Quantitative Trait ◽  
Acute Decompensated Heart Failure ◽  
Decompensated Heart Failure ◽  
Ang Ii ◽  
High Salt Diet ◽  
Salt Diet ◽  
Filial Generation

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.

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.

Abstract P328: Angiotensin II Inhibits the High Salt-induced Production of Sphigosine-1-phosphate in the Renal Medulla

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Weili Wang ◽  
Junping Hu ◽  
Pin-Lan Li ◽  
Justin L Poklis ◽  
Ningjun Li
Keyword(s):  
Angiotensin Ii ◽  
Renal Medulla ◽  
High Salt ◽  
Ang Ii ◽  
Male Adult ◽  
High Salt Diet ◽  
Salt Diet ◽  
Protein Levels ◽  
Medullary Tissue ◽  
Natriuretic Effect

We have previously shown that sphigosine-1-phosphate (S1P) produces natriuretic effects via activation of S1P receptor 1 in the renal medulla and that this natriuretic effect may be through inhibition of epithelial sodium channel. The present study examined the expression of the enzymes that produce S1P in the renal medullary tissue and tested the hypothesis that angiotensin II (ANG II) reduces the expression of S1P-producing enzyme and thereby the levels of S1P in the renal medulla. Male adult C56BL/6 mice, 10-12 weeks old, were treated with a low salt diet (LS, 0.4%), high salt diet (HS, 4% NaCl) or HS + ANG II (600ng/kg/min, S.C.) for 10 days. A high salt diet increased the level of S1P, whereas ANG II significantly inhibited the HS-induced increase of S1P levels in the renal medullary tissue. The levels of S1P were 6.6 ± 0.34, 11.4 ± 1.33 and 3.5 ± 0.49 pmol/mg of tissue in LS, HS and HS + ANG II group, respectively. There were no difference in the levels of sphingosine kinase 1 (SPHK1), the enzyme that produces S1P by phosphorylating sphingosine, among the different groups of mice by Western blot analysis. However, a high salt diet increased the protein levels of acid ceramidase (ACDase), an upstream enzyme that produces sphingosine, the substrate for SPHK1. This HS-induced increase in ACDase was inhibited by ANG II. The relative protein levels of ACDase were 1.0 ± 0.07, 1.4 ± 0.07 and 0.17 ± 0.11 in LS, HS and HS + ANG II group, respectively. These results demonstrated that a high salt diet increased the levels of S1P in the renal medulla, probably by increasing the level of one of the S1P-producing enzymes ACDase, and that ANG II reduced the levels of ACDase and S1P in the renal medulla. Given the diuretic effect of S1P, ANG II-induced reduction of S1P production in the renal medulla may be a mechanism contributing to the sodium retention and hypertension associated with excessive ANG II. (Support: NIH grant HL89563)

scholarly journals Dietary Fructose Increases the Sensitivity of Proximal Tubules to Angiotensin II in Rats Fed High-Salt Diets

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1244 ◽  
Author(s):  
Agustin Gonzalez-Vicente ◽  
Nancy Hong ◽  
Nianxin Yang ◽  
Pablo Cabral ◽  
Jessica Berthiaume ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Tap Water ◽  
Transport Processes ◽  
High Salt ◽  
Proximal Tubules ◽  
Ang Ii ◽  
High Salt Diet ◽  
Salt Diet ◽  
Dietary Fructose ◽  
Salt Sensitive Hypertension

Dietary fructose causes salt-sensitive hypertension. Proximal tubules (PTs) reabsorb 70% of the filtered NaCl. Angiotensin II (Ang II), atrial natriuretic peptide (ANP) and norepinephrine (NE) regulate this process. Although Ang II signaling blockade ameliorates fructose-induced salt-sensitive hypertension, basal PT Na+ reabsorption and its sensitivity to the aforementioned factors have not been studied in this model. We hypothesized consuming fructose with a high-salt diet selectively enhances the sensitivity of PT transport to Ang II. We investigated the effects of Ang II, ANP and NE on PT Na reabsorption in rats fed a high-salt diet drinking tap water (HS) or 20% fructose (HS-FRU). Oxygen consumption (QO2) was used as a measure of all ATP-dependent transport processes. Na+/K+-ATPase and Na+/H+-exchange (NHE) activities were studied because they represent primary apical and basolateral transporters in this segment. The effect of 10−12 mol/L Ang II in QO2 by PTs from HS-FRU was larger than HS (p < 0.02; n = 7). In PTs from HS-FRU 10−12 mol/L Ang II stimulated NHE activity by 2.6 ± 0.7 arbitrary fluorescence units/s (p < 0.01; n = 5) but not in those from HS. The stimulatory effect of Ang II on PT Na+/K+-ATPase activity was not affected by HS-FRU. Responses of QO2 and NHE activity to ANP did not differ between groups. The response of QO2 to NE was unaltered by HS-FRU. We concluded that the sensitivity of PT Na+ reabsorption specifically to Ang II is enhanced by HS-FRU. This maintains high rates of transport even in the presence of low concentrations of the peptide, and likely contributes to the hypertension.

Renal endothelin in chronic angiotensin II hypertension

2002 ◽  
Vol 283 (1) ◽  
pp. R243-R248 ◽  
Author(s):  
Jennifer M. Sasser ◽  
Jennifer S. Pollock ◽  
David M. Pollock
Keyword(s):  
Sodium Intake ◽  
Renal Tissue ◽  
High Salt ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Outer Medulla ◽  
High Salt Diet ◽  
Salt Diet ◽  
Sprague Dawley Rats ◽  
Saline Vehicle

To determine the influence of chronic ANG II infusion on urinary, plasma, and renal tissue levels of immunoreactive endothelin (ET), ANG II (65 ng/min) or saline vehicle was delivered via osmotic minipump in male Sprague-Dawley rats given either a high-salt diet (10% NaCl) or normal-salt diet (0.8% NaCl). High-salt diet alone caused a slight but not statistically significant increase (7 ± 1%) in mean arterial pressure (MAP). MAP was significantly increased in ANG II-infused rats (41 ± 10%), and the increase in MAP was significantly greater in ANG II rats given a high-salt diet (59 ± 1%) compared with the increase observed in rats given a high-salt diet alone or ANG II infusion and normal-salt diet. After a 2-wk treatment, urinary excretion of immunoreactive ET was significantly increased by ∼50% in ANG II-infused animals and by over 250% in rats on high-salt diet, with or without ANG II infusion. ANG II infusion combined with high-salt diet significantly increased immunoreactive ET content in the cortex and outer medulla, but this effect was not observed in other groups. In contrast, high-salt diet, with or without ANG II infusion, significantly decreased immunoreactive ET content within the inner medulla. These data indicate that chronic elevations in ANG II levels and sodium intake differentially affect ET levels within the kidney and provide further support for the hypothesis that the hypertensive effects of ANG II may be due to interaction with the renal ET system.

scholarly journals AT1 receptor participates in the cardiac hypertrophy induced by resistance training in rats

2008 ◽  
Vol 295 (2) ◽  
pp. R381-R387 ◽  
Author(s):  
Valerio G. Barauna ◽  
Flávio C. Magalhaes ◽  
Jose E. Krieger ◽  
Edilamar M. Oliveira
Keyword(s):  
Resistance Training ◽  
Left Ventricle ◽  
Cardiac Hypertrophy ◽  
Receptor Gene ◽  
Weight Ratio ◽  
High Salt ◽  
Receptor Expression ◽  
Ang Ii ◽  
High Salt Diet ◽  
Salt Diet

Resistance training is accompanied by cardiac hypertrophy, but the role of the renin-angiotensin system (RAS) in this response is elusive. We evaluated this question in 36 male Wistar rats divided into six groups: control ( n = 6); trained ( n = 6); control + losartan (10 mg·kg−1·day−1, n = 6); trained + losartan ( n = 6); control + high-salt diet (1%, n = 6); and trained + high-salt diet (1%, n = 6). High salt was used to inhibit the systemic RAS and losartan to block the AT1 receptor. The exercise protocol consisted of: 4 × 12 bouts, 5×/wk during 8 wk, with 65–75% of one repetition maximum. Left ventricle weight-to-body weight ratio increased only in trained and trained + high-salt diet groups (8.5% and 10.6%, P < 0.05) compared with control. Also, none of the pathological cardiac hypertrophy markers, atrial natriuretic peptide, and αMHC (α-myosin heavy chain)-to-βMHC ratio, were changed. ACE activity was analyzed by fluorometric assay (systemic and cardiac) and plasma renin activity (PRA) by RIA and remained unchanged upon resistance training, whereas PRA decreased significantly with the high-salt diet. Interestingly, using Western blot analysis and RT-PRC, no changes were observed in cardiac AT2 receptor levels, whereas the AT1 receptor gene (56%, P < 0.05) and protein (31%, P < 0.05) expressions were upregulated in the trained group. Also, cardiac ANG II concentration evaluated by ELISA remained unchanged (23.27 ± 2.4 vs. 22.01 ± 0.8 pg/mg, P > 0.05). Administration of a subhypotensive dose of losartan prevented left ventricle hypertrophy in response to the resistance training. Altogether, we provide evidence that resistance training-induced cardiac hypertrophy is accompanied by induction of AT1 receptor expression with no changes in cardiac ANG II, which suggests a local activation of the RAS consistent with the hypertrophic response.

Th-W51:3 High salt diet accelerates atherosclerosis in ApoE-/- mice with fixed high angiotensin II levels

2006 ◽  
Vol 7 (3) ◽  
pp. 469 ◽  
Author(s):  
M.E. Johansson ◽  
E. Bernberg ◽  
I.J. Andersson ◽  
L. Gan ◽  
G. Bergström
Keyword(s):  
Angiotensin Ii ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet
Sign in / Sign up

Export Citation Format

Share Document