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.

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.

scholarly journals Effects of Renin-Angiotensin System Inhibitors on Renal Expression of Renalase in Sprague-Dawley Rats Fed With High Salt Diet

2015 ◽  
Vol 40 (6) ◽  
pp. 605-613 ◽  
Author(s):  
Yang Wang ◽  
Bing-Qing Xie ◽  
Wei-Hua Gao ◽  
Ding-Yi Yan ◽  
Wen-Ling Zheng ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
High Salt ◽  
Sprague Dawley ◽  
High Salt Diet ◽  
Angiotensin System ◽  
Salt Diet ◽  
Renin Angiotensin ◽  
Sprague Dawley Rats ◽  
Renal Expression

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.

Effect of a perinatal high-salt diet on blood pressure control mechanisms in young Sprague-Dawley rats

2004 ◽  
Vol 286 (4) ◽  
pp. R764-R770 ◽  
Author(s):  
Steven J. Swenson ◽  
Robert C. Speth ◽  
James P. Porter
Keyword(s):  
Blood Pressure ◽  
Nervous Activity ◽  
Receptor Activation ◽  
High Salt ◽  
Early Age ◽  
Sprague Dawley ◽  
Baroreflex Control ◽  
High Salt Diet ◽  
Salt Diet ◽  
Sprague Dawley Rats

In the present investigation we sought to determine if a perinatal high-salt treatment affects blood pressure at an early age (30 days), and if so, to determine the mechanisms responsible for the hypertension. Pregnant dams were given an 8% NaCl diet [high-salt (HS) rats] during the final one-third of gestation and throughout the suckling period. After weaning, the pups continued to receive the high-salt diet until testing at age 30 days. Control groups received a normal-salt diet (NS rats). In HS rats, mean arterial pressure (MAP) was significantly increased (110 ± 5 vs. 96 ± 3 mmHg) compared with NS rats. Blockade of brain AT1 receptors with intracerebroventricular losartan decreased MAP in HS but not NS rats. Blockade of α-adrenergic receptors with intravenous phentolamine or ganglionic transmission with intravenous chlorisondamine produced a greater decrease in MAP in HS rats. Baroreflex control of heart rate was assessed using a four-parameter logistics function. The mid-range MAP (p3) was significantly increased in the HS rats. No other baroreflex parameters were affected. Specific binding of 125I-[Sar1,Ile8]ANG II to AT1 receptors was increased in the subfornical organ (SFO) of the HS rats. Expression of AT1a receptor mRNA was greater in both SFO and PVN of the HS rats. These data suggest that even at an early age, Sprague-Dawley rats treated with a perinatal high-salt diet are hypertensive. The elevated blood pressure appears to be caused by increased sympathetic nervous activity, resulting, in part, from increased brain AT1 receptor activation.

Evidence for endothelin involvement in the response to high salt

2001 ◽  
Vol 281 (1) ◽  
pp. F144-F150 ◽  
Author(s):  
David M. Pollock ◽  
Jennifer S. Pollock
Keyword(s):  
Blood Pressure ◽  
Receptor Activation ◽  
Blood Pressure Regulation ◽  
High Salt ◽  
Pressure Regulation ◽  
Sprague Dawley ◽  
High Salt Diet ◽  
Salt Loading ◽  
Salt Diet ◽  
Low Salt

Recent evidence suggests that endothelin-1 (ET-1), perhaps through the ETB receptor, may participate in blood pressure regulation through the control of sodium excretion. Mean arterial pressure (MAP) was continuously measured via telemetry implants in male Sprague-Dawley rats. After 1 wk of baseline measurements, rats were given either high (10%) or low (0.08%) NaCl in chow for the remainder of the experiment ( n = 5 in each group). MAP was significantly increased in rats on a high-salt diet (115 ± 2 mmHg) compared with rats on the low-salt diet (103 ± 2 mmHg; P < 0.05). All rats were then treated with the ETB receptor antagonist A-192621 mixed with the food and adjusted daily to ensure a dose of 30 mg · kg−1 · day−1. ETB blockade produced an increase in MAP within a few hours of treatment and was significantly higher in rats on the high-salt diet over a 1-wk period (170 ± 3 vs. 115 ± 3 mmHg, P < 0.01). To determine whether the increase in MAP during A-192621 treatment was due to increased ETA receptor activation, all rats were then given the ETA-selective antagonist ABT-627 in the drinking water while a low-salt/high-salt diet and ETB blockade were continued. ABT-627 decreased MAP within a few hours in rats on either the high-salt (113 ± 3 mmHg) or low-salt (101 ± 3 mmHg) diet. These results support the hypothesis that endothelin, through the ETB receptor, participates in blood pressure regulation in the response to salt loading.

scholarly journals Effects of Doenjang, a Traditional Korean Soybean Paste, with High-Salt Diet on Blood Pressure in Sprague–Dawley Rats

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2745 ◽  
Author(s):  
Eun-Gyung Mun ◽  
Jung Eun Park ◽  
Youn-Soo Cha
Keyword(s):  
Blood Pressure ◽  
Reduce Blood Pressure ◽  
Fermented Food ◽  
High Salt ◽  
Fermented Foods ◽  
Sprague Dawley ◽  
High Salt Diet ◽  
Salt Diet ◽  
Sd Rats ◽  
Soybean Paste

Fermented foods in Korea contain a lot of salt. Although salt is reported to exacerbate health trouble, fermented foods have beneficial effects. We hypothesized that doenjang could reduce blood pressure in Sprague–Dawley (SD) rats fed a high-salt diet. Eighteen SD rats were divided into three groups: normal-salt (NS) group, high-salt (HS) group, and high-salt with doenjang (HSD) group. The salinity of doenjang and saltwater was adjusted to 8% using Mohr’s method. Blood pressure was significantly reduced in the HSD group compared with the HS group. Water intake and urine excretion volume has significantly increased in the HS group compared with the HSD group. The excreted concentrations of urine sodium, urine potassium, and feces potassium significantly increased in the HSD group compared with the HS and NS groups. Renin level was significantly decreased in the HSD group compared to the other groups. These results indicate that eating traditional salty fermented food is not a direct cause of hypertension, and the intake of doenjang in normal healthy animals improved blood pressure.

scholarly journals Metabolic Syndrome and Salt-Sensitive Hypertension in Polygenic Obese TALLYHO/JngJ Mice: Role of Na/K-ATPase Signaling

2019 ◽  
Vol 20 (14) ◽  
pp. 3495 ◽  
Author(s):  
Yanling Yan ◽  
Jiayan Wang ◽  
Muhammad A. Chaudhry ◽  
Ying Nie ◽  
Shuyan Sun ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Significant Rise ◽  
Protein Carbonylation ◽  
High Salt ◽  
Kidney Cortex ◽  
High Salt Diet ◽  
Salt Diet ◽  
Salt Sensitive Hypertension

We have demonstrated that Na/K-ATPase acts as a receptor for reactive oxygen species (ROS), regulating renal Na+ handling and blood pressure. TALLYHO/JngJ (TH) mice are believed to mimic the state of obesity in humans with a polygenic background of type 2 diabetes. This present work is to investigate the role of Na/K-ATPase signaling in TH mice, focusing on susceptibility to hypertension due to chronic excess salt ingestion. Age-matched male TH and the control C57BL/6J (B6) mice were fed either normal diet or high salt diet (HS: 2, 4, and 8% NaCl) to construct the renal function curve. Na/K-ATPase signaling including c-Src and ERK1/2 phosphorylation, as well as protein carbonylation (a commonly used marker for enhanced ROS production), were assessed in the kidney cortex tissues by Western blot. Urinary and plasma Na+ levels were measured by flame photometry. When compared to B6 mice, TH mice developed salt-sensitive hypertension and responded to a high salt diet with a significant rise in systolic blood pressure indicative of a blunted pressure-natriuresis relationship. These findings were evidenced by a decrease in total and fractional Na+ excretion and a right-shifted renal function curve with a reduced slope. This salt-sensitive hypertension correlated with changes in the Na/K-ATPase signaling. Specifically, Na/K-ATPase signaling was not able to be stimulated by HS due to the activated baseline protein carbonylation, phosphorylation of c-Src and ERK1/2. These findings support the emerging view that Na/K-ATPase signaling contributes to metabolic disease and suggest that malfunction of the Na/K-ATPase signaling may promote the development of salt-sensitive hypertension in obesity. The increased basal level of renal Na/K-ATPase-dependent redox signaling may be responsible for the development of salt-sensitive hypertension in polygenic obese TH mice.

Endothelin B receptors impair baroreflex function and increase blood pressure variability during high salt diet

2021 ◽  
pp. 102796
Author(s):  
Bryan K. Becker ◽  
Jermaine G. Johnston ◽  
Carolyn Young ◽  
Alfredo A. Torres Rodriguez ◽  
Chunhua Jin ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Variability ◽  
High Salt ◽  
Increase Blood Pressure ◽  
High Salt Diet ◽  
Salt Diet ◽  
Baroreflex Function ◽  
Endothelin B
Sign in / Sign up

Export Citation Format

Share Document