High Salt Diet Induces HDAC1‐Dependent Disruption of Nitric Oxide Signaling in the Renal Microvasculature

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Luke S Dunaway ◽  
Anthony K Cook ◽  
David M Pollock ◽  
Kelly A Hyndman ◽  
Edward W Inscho ◽  
...  
2020 ◽  
Vol 319 (1) ◽  
pp. R87-R95
Author(s):  
Ankit Gilani ◽  
Kevin Agostinucci ◽  
Jonathan V. Pascale ◽  
Sakib Hossain ◽  
Sharath Kandhi ◽  
...  

20-Hydroxyeicosatetraenoic acid (20-HETE) has been linked to blood pressure (BP) regulation via actions on the renal microvasculature and tubules. We assessed the tubular 20-HETE contribution to hypertension by generating transgenic mice overexpressing the CYP4A12-20-HETE synthase (PT-4a12 mice) under the control of the proximal tubule (PT)-specific promoter phosphoenolpyruvate carboxykinase (PEPCK). 20-HETE levels in the kidney cortex of male (967 ± 210 vs. 249 ± 69 pg/mg protein) but not female (121 ± 15 vs. 92 ± 11 pg/mg protein) PT-4a12 mice showed a 2.5-fold increase compared with wild type (WT). Renal cortical Cyp4a12 mRNA and CYP4A12 protein in male but not female PT-4a12 mice increased by two- to threefold compared with WT. Male PT-4a12 mice displayed elevated BP (142 ± 1 vs. 111 ± 4 mmHg, P < 0.0001), whereas BP in female PT-4a12 mice was not significantly different from WT (118 ± 2 vs. 117 ± 2 mmHg; P = 0.98). In male PT-4a12 mice, BP decreased when mice were transitioned from a control-salt (0.4%) to a low-salt diet (0.075%) from 135 ± 4 to 120 ± 6 mmHg ( P < 0.01) and increased to 153 ± 5 mmHg ( P < 0.05) when mice were placed on a high-salt diet (4%). Female PT-4a12 mice did not show changes in BP on either low- or high-salt diet. In conclusion, the expression of Cyp4a12 driven by the PEPCK promoter is sex specific, probably because of its X-linkage. The salt-sensitive hypertension seen in PT-4a12 male mice suggests a potential antinatriuretic activity of 20-HETE that needs to be further explored.


Hypertension ◽  
2001 ◽  
Vol 37 (2) ◽  
pp. 516-523 ◽  
Author(s):  
Jena B. Giardina ◽  
GaChavis M. Green ◽  
Anna N. Rinewalt ◽  
Joey P. Granger ◽  
Raouf A. Khalil

2003 ◽  
Vol 474 (2-3) ◽  
pp. 241-247 ◽  
Author(s):  
Olusoga Sofola ◽  
Momoh Yakubu ◽  
Imaculata Igbo ◽  
Mohammad Newaz ◽  
Adebayo Oyekan

2021 ◽  
Author(s):  
Olumide Fadahunsi ◽  
Peter Adegbola ◽  
Olayemi Adebola Akintola ◽  
Bamidele Stephen Ajilore ◽  
olubukola sinbad Olorunnisola

Abstract Consistent consumption of high salt diet (HSD) has been associated with increased cellular generation of free radicals which has been implicated in the derangement of some vital organs and etiology of cardiovascular disorders. This study was designed to investigate the combined effect of some commonly employed medicinal plants on serum lipid profile and antioxidant status of aorta, kidney, and liver of high salt diet-fed animals. Thirty-five male Wistar rats were divided into 5 groups of 7 animals each. Group 1 and 2 animals were fed normal rat and 16 % high salt diet only respectively. Animals in groups 3, 4, and 5 were fed 16% high salt diet with 800, 400, and 200 mg/kg bw poly-herbal extract (PHE) respectively once for 28 consecutive days. Serum low-density lipoprotein (LDL), triacylglycerol (TG), total cholesterol (TC) and high-density lipoprotein (HDL), malondialdehyde, nitric oxide, catalase, superoxide dismutase, glutathione peroxidase, glutathione concentration, and activities were assessed in the aorta, kidney, and liver. PHE (p < 0.05) significantly reduced malondialdehyde and nitric oxide concentration and increased antioxidant enzymes and glutathione activity. Elevated serum TG, TC, LDL, and TC content in HSD-fed animals were significantly (p < 0.05) reduced to normal in PHE-treated rats while HDL was significantly elevated (p < 0.05) in a concentration-dependent manner in PHE treated animals. Feeding with PHE attenuated high salt diet imposed derangement in serum lipid profile and antioxidant status in the organs of the experimental rats.


Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Jorge E Celedonio ◽  
Victor C Nwazue ◽  
Emily M Garland ◽  
Cyndya A Shibao ◽  
Luis E Okamoto ◽  
...  

Background: Postural tachycardia syndrome (POTS) is characterized by an increase in sympathetic activity, with an exaggerated rise in heart rate upon standing and symptoms of cerebral hypoperfusion. Endothelial/Nitric Oxide (NO) dysfunction might be involved in POTS pathophysiology. As part of the non-pharmacologic treatment of POTS, a high sodium diet is often recommended to increase plasma volume. We assessed endothelial/NO function in conduit vessels (using flow-mediated dilation, FMD) and resistance vessels (using finger pulse arterial tonometry, PAT) in POTS patients during high and low salt diets. Methods: In 14 female POTS patients (34±9 years, BMI 23±3 kg/m 2 ) and 13 matched healthy control subjects (29±4 years, BMI 24±3 kg/m 2 ), we evaluated the time course responses to FMD and PAT. Subjects were randomly assigned to either high salt diet (300mEq/day) or low salt diet (10mEq/day) for 6 days and crossed over to the other arm after 1 month. The areas under the curve for brachial artery diameter by FMD and finger artery dilation by PAT were compared between interventions and groups. Results: No differences in NO function in a conduit artery were seen. In contrast, in resistance vessels, high salt diet increased vasodilation in both POTS and healthy subjects (figure). In addition, POTS patients have greater vasodilation than healthy subjects during both low and high salt diets (p=0.036 and 0.033 for high and salt diets respectively). Conclusions: POTS patients may have an exaggerated NO response to reactive hyperemia in resistance vessels, but not in conductance vessels. This excessive vasodilation could contribute to POTS symptoms on standing.


2017 ◽  
Vol 22 (4) ◽  
pp. 765-769
Author(s):  
Ayoola I. Olushola ◽  
Komolafe O. Aderibigbe ◽  
Saka O. Stephen ◽  
Odukoya S. Ayodeji

Background. The cardioprotective effects of Persea americana extract was investigated on biochemical activities of high salt–fed adult Wistar rats in this study. Method. Forty healthy Wistar rats of both sexes weighing 120 to 150 g were randomly assigned into 8 groups of 5 rats each (groups A, B, C, D, E, F, G, and H). Rats in groups A, F, G, and H were fed with standard laboratory pellets, while groups B, C, D, and E were fed on the high-salt diet for 4 weeks. Concomitantly, daily administration of 50, 100, and 150 mg/kg of the P americana extract were given orally to groups C and F, D and G, and E and H, respectively, while rats in groups A and B were administered distilled water. Blood samples were taken by cardiac puncture; concentration of sodium ion, potassium ion, nitric oxide, and activity of lactate dehydrogenase were determined. One-way analysis of variance was used to analyze data, followed by Student-Newman-Keuls (SNK) test for multiple comparison. Results. Results revealed that concentration of potassium ion and nitric oxide was significantly lower ( P < .05) in high salt–fed groups. Sodium ion concentration and activity of lactate dehydrogenase were higher in high salt–fed group while P americana prevented biochemical perturbations in other experimental groups. Conclusion. In conclusion, high salt–diet induced biochemical alterations which were significantly protected by oral administration of P americana extract.


Medicines ◽  
2021 ◽  
Vol 8 (6) ◽  
pp. 25
Author(s):  
Olubukola Sinbad Olorunnisola ◽  
Peter Ifeoluwa Adegbola ◽  
Bamidele Stephen Ajilore ◽  
Olayemi Adebola Akintola ◽  
Olumide Samuel Fadahunsi

Consistent consumption of high salt diet (HSD) has been associated with increased cellular generation of free radicals, which has been implicated in the derangement of some vital organs and etiology of cardiovascular disorders. This study was designed to investigate the combined effect of some commonly employed medicinal plants on serum lipid profile and antioxidant status of aorta, kidney, and liver of high salt diet-fed animals. Out of the total fifty male Wistar rats obtained, fifteen were used for acute toxicity study, while the remaining thirty-five were divided into 5 groups of 7 animals each. Group 1 and 2 animals were fed normal rat chow (NRC) and 16% high salt diet (HSD) only, respectively. Animals in groups 3, 4 and 5 were fed 16% HSD with 800, 400, and 200 mg/kg bw poly-herbal extract (PHE), respectively, once for 28 consecutive days. Serum low-density lipoprotein (LDL), triacylglycerol (TG), total cholesterol (TC) and high-density lipoprotein (HDL), malondialdehyde, nitric oxide, catalase, superoxide dismutase, glutathione peroxidase, glutathione concentration, and activities were assessed in the aorta, kidney, and liver. Poly-herbal extract (p < 0.05) significantly reduced malondialdehyde and nitric oxide concentrations and also increased antioxidant enzymes and glutathione activity. Elevated serum TG, TC, LDL, and TC content in HSD-fed animals were significantly (p < 0.05) reduced to normal in PHE-treated rats while HDL was significantly elevated (p < 0.05) in a concentration-dependent manner in PHE treated animals. Feeding with PHE attenuated high-salt diet imposed derangement in serum lipid profile and antioxidant status in the organs of the experimental rats.


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