Interleukin‐1 in chronic angiotensin II‐high salt diet induced hypertension

Recent evidence suggests that salt-sensitive hypertension develops as a consequence of renal infiltration with immunocompetent cells. We investigated whether proteinuria, which is known to induce interstitial nephritis, causes salt-sensitive hypertension. Female Lewis rats received 2 g of BSA intraperitoneally daily for 2 wk. After protein overload (PO), 6 wk of a high-salt diet induced hypertension [systolic blood pressure (SBP) = 156 ± 11.8 mmHg], whereas rats that remained on a normal-salt diet and control rats (without PO) on a high-salt diet were normotensive. Administration of mycophenolate mofetil (20 mg · kg−1 · day−1) during PO resulted in prevention of proteinuria-related interstitial nephritis, reduction of renal angiotensin II-positive cells and oxidative stress (superoxide-positive cells and renal malondialdehyde content), and resistance to the hypertensive effect of the high-salt diet (SBP = 129 ± 12.2 mmHg). The present studies support the participation of renal inflammatory infiltrate in the pathogenesis of salt-sensitive hypertension and provide a direct link between two risk factors of progressive renal damage: proteinuria and hypertension.

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Urinary excretion of angiotensinogen in male and female Sprague Dawley rats during angiotensin II infusion and high salt diet

The FASEB Journal ◽

10.1096/fasebj.24.1_supplement.1024.28 ◽

2010 ◽

Vol 24 (S1) ◽

Author(s):

Vicky F. Rands ◽

Charlene Byrd ◽

Dale Seth ◽

Hiroyuki Kobori ◽

Minolfa C Prieto

Keyword(s):

Angiotensin Ii ◽

Urinary Excretion ◽

High Salt ◽

Sprague Dawley ◽

High Salt Diet ◽

Salt Diet ◽

Male And Female ◽

Sprague Dawley Rats

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

Atherosclerosis Supplements ◽

10.1016/s1567-5688(06)81881-7 ◽

2006 ◽

Vol 7 (3) ◽

pp. 469 ◽

Cited By ~ 1

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

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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.

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Intestinal Flora Modulates Blood Pressure by Regulating the Synthesis of Intestinal-Derived Corticosterone in High Salt-Induced Hypertension

Circulation Research ◽

10.1161/circresaha.119.316394 ◽

2020 ◽

Vol 126 (7) ◽

pp. 839-853 ◽

Cited By ~ 6

Author(s):

Xuefang Yan ◽

Jiajia Jin ◽

Xinhuan Su ◽

Xianlun Yin ◽

Jing Gao ◽

...

Keyword(s):

Blood Pressure ◽

Arachidonic Acid ◽

Fecal Microbiota Transplantation ◽

Intestinal Flora ◽

Corticosterone Level ◽

Fecal Microbiota ◽

High Salt ◽

High Salt Diet ◽

Salt Diet ◽

Induced Hypertension

Rationale: High-salt diet is one of the most important risk factors for hypertension. Intestinal flora has been reported to be associated with high salt–induced hypertension (hSIH). However, the detailed roles of intestinal flora in hSIH pathogenesis have not yet been fully elucidated. Objective: To reveal the roles and mechanisms of intestinal flora in hSIH development. Methods and Results: The abovementioned issues were investigated using various techniques including 16S rRNA gene sequencing, untargeted metabolomics, selective bacterial culture, and fecal microbiota transplantation. We found that high-salt diet induced hypertension in Wistar rats. The fecal microbiota of healthy rats could dramatically lower blood pressure (BP) of hypertensive rats, whereas the fecal microbiota of hSIH rats had opposite effects. The composition, metabolism, and interrelationship of intestinal flora in hSIH rats were considerably reshaped, including the increased corticosterone level and reduced Bacteroides and arachidonic acid levels, which tightly correlated with BP. The serum corticosterone level was also significantly increased in rats with hSIH. Furthermore, the above abnormalities were confirmed in patients with hypertension. The intestinal Bacteroides fragilis could inhibit the production of intestinal-derived corticosterone induced by high-salt diet through its metabolite arachidonic acid. Conclusions: hSIH could be transferred by fecal microbiota transplantation, indicating the pivotal roles of intestinal flora in hSIH development. High-salt diet reduced the levels of B fragilis and arachidonic acid in the intestine, which increased intestinal-derived corticosterone production and corticosterone levels in serum and intestine, thereby promoting BP elevation. This study revealed a novel mechanism different from inflammation/immunity by which intestinal flora regulated BP, namely intestinal flora could modulate BP by affecting steroid hormone levels. These findings enriched the understanding of the function of intestinal flora and its effects on hypertension.

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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.

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Role of central nervous system aldosterone synthase and mineralocorticoid receptors in salt-induced hypertension in Dahl salt-sensitive rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.90903.2008 ◽

2009 ◽

Vol 296 (4) ◽

pp. R994-R1000 ◽

Cited By ~ 66

Author(s):

Bing S. Huang ◽

Roselyn A. White ◽

Arco Y. Jeng ◽

Frans H. H. Leenen

Keyword(s):

Salt Intake ◽

High Salt ◽

High Salt Diet ◽

Salt Diet ◽

Aldosterone Synthase ◽

High Salt Intake ◽

Induced Hypertension ◽

Synthase Inhibitor ◽

The Brain

In Dahl salt-sensitive (S) rats, high salt intake increases cerebrospinal fluid (CSF) Na+ concentration ([Na+]) and blood pressure (BP). Intracerebroventricular (ICV) infusion of a mineralocorticoid receptor (MR) blocker prevents the hypertension. To assess the role of aldosterone locally produced in the brain, we evaluated the effects of chronic central blockade with the aldosterone synthase inhibitor FAD286 and the MR blocker spironolactone on changes in aldosterone and corticosterone content in the hypothalamus and the increase in CSF [Na+] and hypertension induced by high salt intake in Dahl S rats. After 4 wk of high salt intake, plasma aldosterone and corticosterone were not changed, but hypothalamic aldosterone increased by ∼35% and corticosterone tended to increase in Dahl S rats, whereas both steroids decreased by ∼65% in Dahl salt-resistant rats. In Dahl S rats fed the high-salt diet, ICV infusion of FAD286 or spironolactone did not affect the increase in CSF [Na+]. ICV infusion of FAD286 prevented the increase in hypothalamic aldosterone and 30 mmHg of the 50-mmHg BP increase induced by high salt intake. ICV infusion of spironolactone fully prevented the salt-induced hypertension. These results suggest that, in Dahl S rats, high salt intake increases aldosterone synthesis in the hypothalamus and aldosterone acts as the main MR agonist activating central pathways contributing to salt-induced hypertension.

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