Effect of peroxisome proliferator-activated receptor-α siRNA on hypertension and renal injury in the rat following nitric oxide withdrawal and high salt diet

2009 ◽  
Vol 27 (11) ◽  
pp. 2223-2231 ◽  
Author(s):  
Mohammad Newaz ◽  
Katsuri Ranganna ◽  
Luan D Truong ◽  
Adebayo Oyekan
Keyword(s):  
Nitric Oxide ◽  
Renal Injury ◽  
High Salt ◽  
Peroxisome Proliferator ◽  
High Salt Diet ◽  
Peroxisome Proliferator Activated Receptor ◽  
Salt Diet

Mycophenolate mofetil prevents salt-sensitive hypertension resulting from nitric oxide synthesis inhibition

2001 ◽  
Vol 281 (1) ◽  
pp. F38-F47 ◽  
Author(s):  
Yasmir Quiroz ◽  
Héctor Pons ◽  
Katherine L. Gordon ◽  
Jaimar Rincón ◽  
Maribel Chávez ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Mycophenolate Mofetil ◽  
Washout Period ◽  
Renal Injury ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Renal Histology ◽  
Salt Sensitive Hypertension

Recent studies have suggested that subtle microvascular and tubulointerstitial injury in the kidney can cause salt-sensitive hypertension. To test this hypothesis, we determined whether the mild renal disease induced by transient blockade of nitric oxide (NO) synthesis would result in salt-sensitive hypertension and whether prevention of the renal injury by coadministration of the immunosuppressive agent mycophenolate mofetil (MMF) would block the development of salt sensitivity. N ω-nitro-l-arginine-methyl ester (l-NAME; 70 mg/100 ml in the drinking water) was administered for 3 wk to rats with or without MMF (30 mg · kg−1 · day−1 by gastric gavage), followed by a 1-wk “washout” period in which the MMF was continued, which was followed in turn by placement on a high-salt (4% NaCl) diet for an additional 4 wk. Renal histology was examined at 3 and 8 wk, and blood pressure was measured serially.l-NAME treatment resulted in acute hypertension and the development of mild renal injury. During the washout period, blood pressure returned to normal, only to return to the hypertensive range on exposure of the animals to a high-salt diet. MMF treatment prevented the development of hypertension in response to a high-salt diet. This correlated with the ability of MMF to inhibit specific aspects of the renal injury, including the development of segmental glomerulosclerosis, the infiltration of T cells and ANG II-positive cells, and the thickening of afferent arterioles.

Abstract 16835: Targeted Disruption of Paraoxonase 3 in a Dahl Salt-Sensitive Rat Model of Chronic Kidney Disease Increases Renal Cortical Pro-Inflammatory Eicosanoids

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Chrysan J Mohammed ◽  
Fatimah K Khalaf ◽  
Prabhatchandra Dube ◽  
Tyler J Reid ◽  
Jacob A Connolly ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Injury ◽  
Renal Cortex ◽  
High Salt ◽  
High Density Lipoproteins ◽  
Wild Type ◽  
Targeted Disruption ◽  
High Salt Diet ◽  
Salt Diet ◽  
Mediators Of Inflammation

Background: Paraoxonase 3 (Pon3), is one of the three isoforms of the paraoxonase gene family. While Pon1 and Pon2 are widely studied, there is a paucity of knowledge regarding Pon3. Pon3 is synthesized in the liver and can circulate bound to high-density lipoproteins. There is significant expression in the kidney also. Pon3 has the ability to metabolize eicosanoids, which can act as signaling molecules and have known roles in the pathophysiology of some renal diseases. Decreased Pon activity is associated with elevated levels of eicosanoid metabolites and adverse clinical outcomes. We tested the hypothesis that targeted disruption of Pon3 results in elevated levels of pro-inflammatory eicosanoids and progression of renal injury. Methods/ Results: Ten week old male Dahl salt-sensitive (SS rats) and Pon3 mutant rats (SS Pon3 KO) were maintained on 8% high salt diet for eight weeks, to initiate salt-sensitive hypertensive renal disease. Previously we observed that SS Pon3 KO rats on eight weeks high salt diet demonstrated significantly increased phenotypic renal injury and mortality. In the current study, we noted that SS Pon3 KO had significantly decreased (p<0.05) glomerular filtration rate compared to SS wild type. Blood pressure (radiotelemetry) as well as plasma angiotensin and aldosterone (LC-MS/MS) were not different between the two groups after high salt diet. We used targeted lipidomic profiling to determine eicosanoid content in renal cortex from SS Pon3 KO and SS wild type rats at the end of eight weeks of high salt diet. We found that hydroxyl fatty acids 5-HEPE and 5-HETE (5-lipoxygenase dependent arachidonic acid metabolites) were significantly (p<0.05) elevated in the renal cortex of SS Pon3 KO compared to SS wild type rats. In addition to being mediators of inflammation, these metabolites are associated with renal cell injury and death. Furthermore, prostaglandin 6-keto-PGF 1α , which has known links to renal inflammation, was significantly (p<0.05) increased in renal cortex of SS- Pon3 KO compared to SS wild type rats. Conclusion: These findings suggest that targeted deletion of Pon3 increases pro-inflammatory eicosanoids (5-HETE and 5-HEPE) and prostaglandins (6-keto-PGF 1α ), as well as increases renal damage independent of blood pressure.

scholarly journals Association of a Disrupted Dipping Pattern of Blood Pressure with Progression of Renal Injury during the Development of Salt-Dependent Hypertension in Rats

2020 ◽  
Vol 21 (6) ◽  
pp. 2248 ◽  
Author(s):  
Abu Sufiun ◽  
Asadur Rahman ◽  
Kazi Rafiq ◽  
Yoshihide Fujisawa ◽  
Daisuke Nakano ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Circadian Rhythm ◽  
Renal Injury ◽  
Tissue Injury ◽  
Renal Tissue ◽  
High Salt ◽  
Hypertensive Rats ◽  
High Salt Diet ◽  
Salt Diet ◽  
The Difference

The aim of the present study is to investigate whether a disruption of the dipping pattern of blood pressure (BP) is associated with the progression of renal injury in Dahl salt-sensitive (DSS) hypertensive rats. Seven-week-old DSS rats were fed a high salt diet (HSD; 8% NaCl) for 10 weeks, followed by a transition to a normal salt diet (NSD; 0.3% NaCl) for 4 weeks. At baseline, NSD-fed DSS rats showed a dipper-type circadian rhythm of BP. By contrast, HSD for 5 days caused a significant increase in the difference between the active and inactive periods of BP with an extreme dipper type of BP, while proteinuria and renal tissue injury were not observed. Interestingly, HSD feeding for 10 weeks developed hypertension with a non-dipper pattern of BP, which was associated with obvious proteinuria and renal tissue injury. Four weeks after switching to an NSD, BP and proteinuria were significantly decreased, and the BP circadian rhythm returned to the normal dipper pattern. These data suggest that the non-dipper pattern of BP is associated with the progression of renal injury during the development of salt-dependent hypertension.

scholarly journals Role of Endothelin B Receptors in Enhancing Endothelium-Dependent Nitric Oxide–Mediated Vascular Relaxation During High Salt Diet

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
Keyword(s):  
Nitric Oxide ◽  
High Salt ◽  
Vascular Relaxation ◽  
High Salt Diet ◽  
Salt Diet ◽  
Endothelin B

High salt diet modulates cAMP- and nitric oxide-mediated relaxation responses to isoproterenol in the rat aorta

2003 ◽  
Vol 474 (2-3) ◽  
pp. 241-247 ◽  
Author(s):  
Olusoga Sofola ◽  
Momoh Yakubu ◽  
Imaculata Igbo ◽  
Mohammad Newaz ◽  
Adebayo Oyekan
Keyword(s):  
Nitric Oxide ◽  
Rat Aorta ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Relaxation Responses
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