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

2018 ◽  
Vol 36 (4) ◽  
pp. 834-846 ◽  
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

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

1992 ◽  
Vol 83 (1) ◽  
pp. 13-22 ◽  
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.

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

2020 ◽  
Vol 126 (7) ◽  
pp. 839-853 ◽  
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.

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 High Na+ Salt Diet and Remodeling of Vascular Smooth Muscle and Endothelial Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 883
Author(s):  
Ghassan Bkaily ◽  
Yanick Simon ◽  
Ashley Jazzar ◽  
Houssein Najibeddine ◽  
Alexandre Normand ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
High Salt ◽  
Vascular Endothelial ◽  
High Cardiovascular Risk ◽  
High Salt Diet ◽  
Salt Diet ◽  
Lower Survival Rate ◽  
High Sodium ◽  
Induced Hypertension

Our knowledge on essential hypertension is vast, and its treatment is well known. Not all hypertensives are salt-sensitive. The available evidence suggests that even normotensive individuals are at high cardiovascular risk and lower survival rate, as blood pressure eventually rises later in life with a high salt diet. In addition, little is known about high sodium (Na+) salt diet-sensitive hypertension. There is no doubt that direct and indirect Na+ transporters, such as the Na/Ca exchanger and the Na/H exchanger, and the Na/K pump could be implicated in the development of high salt-induced hypertension in humans. These mechanisms could be involved following the destruction of the cell membrane glycocalyx and changes in vascular endothelial and smooth muscle cells membranes’ permeability and osmolarity. Thus, it is vital to determine the membrane and intracellular mechanisms implicated in this type of hypertension and its treatment.

Abstract 446: Deletion of Il-6 Prevents Development of Cardiac Damage and Dysfunction in Chronic Ang Ii-salt-induced Hypertension

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Germán E González ◽  
Nour-Eddine Rhaleb ◽  
Pablo Nakagawa ◽  
Yun-He Liu ◽  
Oscar A Carretero
Keyword(s):  
Blood Pressure ◽  
Cardiac Dysfunction ◽  
High Salt ◽  
Myocardial Inflammation ◽  
Pressure Measurements ◽  
Ang Ii ◽  
Cardiac Damage ◽  
High Salt Diet ◽  
Salt Diet ◽  
Induced Hypertension

IL-6 knockout (KO) mice were reported to spontaneously develop cardiac dysfunction and fibrosis. These KO mice also develop less hypertension when fed high salt and infused with angiotensin II (Ang II). We tested the hypothesis that in IL-6-KO mice the attenuated hypertension in response to Ang II-salt is due to the development of cardiac dysfunction. Male C57Bl/6J and IL-6-/- mice (B6.129S6- Il6 tm1Kopf ) were implanted with telemetry devices for blood pressure measurements, infused with vehicle (V) or Ang II (90 ng/min/mouse subcutaneously) and feed a high salt diet (4% salt diet, HS) for 8 weeks (W). We studied 4 experimental groups: 1) C57BL/6J + V (n=9); 2) IL6-KO + V (n=9); 3) C57BL/6J + Ang II (n=8) and 4) IL6-KO + Ang II (n=6). Blood pressure and echocardiography data were collected before starting the HS diet and Ang II infusion (baseline) and 8 weeks after HS alone or combined with Ang II. Results (Mean±SEM) Conclusion: Our results do not support our hypothesis and shows that the lack of IL-6 does not affect development of hypertension or cardiac hypertrophy but rather prevents cardiac dysfunction, LV dilation, myocardial inflammation and fibrosis in Ang II-salt-induced hypertension, suggesting that IL-6 plays an important role in cardiac dysfunction associated with hypertension.

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

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Erika I Boesen ◽  
Jennifer S Pollock ◽  
David M Pollock
Keyword(s):  
Angiotensin Ii ◽  
Interleukin 1 ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Induced Hypertension

Orchidectomy attenuates impaired endothelial effects of a high-salt diet in Sprague–Dawley rats

2011 ◽  
Vol 89 (4) ◽  
pp. 295-304 ◽  
Author(s):  
A.K. Oloyo ◽  
O.A. Sofola ◽  
C.N. Anigbogu
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Mean Arterial Blood Pressure ◽  
High Salt ◽  
Sprague Dawley ◽  
High Salt Diet ◽  
Salt Diet ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Induced Hypertension

The effect of sex hormones on vascular reactivity is considered one of the underlying factors contributing to gender differences in cardiovascular functions and diseases. Experiments were designed to investigate the role of androgens in salt-induced hypertension by assessing the relaxation response of isolated aortic rings to acetylcholine and sodium nitroprusside in the presence or absence of l-nitroarginine methyl ester in Sprague–Dawley rats. The rats were either orchidectomized or sham-operated, with or without testosterone replacement, and were placed on a normal or high-salt diet for 6 weeks. The results indicate a significant increase (p < 0.001) in the mean arterial blood pressure of rats on the high-salt diet, when compared with control or orchidectomized rats. Orchidectomy elicited a reduction in mean arterial blood pressure (p < 0.01), while testosterone replacement normalized mean arterial blood pressure to values seen in intact rats on the high-salt diet. The high-salt diet reduced the relaxation response to acetylcholine both in the presence and absence of inhibition of endothelial nitric oxide synthase with l-nitroarginine methyl ester. Bilateral orchidectomy attenuated the impaired endothelial function induced by the high-salt diet in rats, but this was reversed by concomitant administration of testosterone, suggesting a role for androgens in enhancing long-term vascular smooth muscle tone and hence maintenance of high blood pressure in salt-induced hypertension.

Heme oxygenase-derived carbon monoxide promotes arteriolar endothelial dysfunction and contributes to salt-induced hypertension in Dahl salt-sensitive rats

2005 ◽  
Vol 288 (3) ◽  
pp. R615-R622 ◽  
Author(s):  
Federico J. Teran ◽  
Robert A. Johnson ◽  
Blake K. Stevenson ◽  
Kelly J. Peyton ◽  
Keith E. Jackson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Carbon Monoxide ◽  
Endothelial Dysfunction ◽  
Heme Oxygenase ◽  
High Salt ◽  
Pressure Effects ◽  
High Salt Diet ◽  
Salt Diet ◽  
Low Salt ◽  
Induced Hypertension

Vascular tissues express heme oxygenase (HO), which metabolizes heme to form carbon monoxide (CO). Heme-derived CO inhibits nitric oxide synthase and promotes endothelium-dependent vasoconstriction. After 4 wk of high-salt diet, Dahl salt-sensitive (Dahl-S) rats display hypertension, increased vascular HO-1 expression, and attenuated vasodilator responses to ACh that can be completely restored by acute treatment with an inhibitor of HO. In this study, we examined the temporal development of HO-mediated endothelial dysfunction in isolated pressurized first-order gracilis muscle arterioles, identified the HO product responsible, and studied the blood pressure effects of HO inhibition in Dahl-S rats on a high-salt diet. Male Dahl-S rats (5–6 wk) were placed on high-salt (8% NaCl) or low-salt (0.3% NaCl) diets for 0–4 wk. Blood pressure increased gradually, and responses to an endothelium-dependent vasodilator, ACh, decreased gradually with the length of high-salt diet. Flow-induced dilation was abolished in hypertensive Dahl-S rats. Acute in vitro pretreatment with an inhibitor of HO, chromium mesoporphyrin (CrMP), restored endothelium-dependent vasodilation and abolished the differences between groups. The HO product CO prevented the restoration of endothelium-dependent dilation by CrMP. Furthermore, administration of an HO inhibitor lowered blood pressure in Dahl-S rats with salt-induced hypertension but did not do so in low-salt control rats. These results suggest that hypertension and HO-mediated endothelial dysfunction develop gradually and simultaneously in Dahl-S rats on high-salt diets. They also suggest that HO-derived CO underlies the impaired endothelial dysfunction and contributes to hypertension in Dahl-S rats on high-salt diets.

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