scholarly journals Impact of obesity on renal structure and function in the presence and absence of hypertension: evidence from melanocortin-4 receptor-deficient mice

2009 ◽  
Vol 297 (3) ◽  
pp. R803-R812 ◽  
Author(s):  
Jussara M. do Carmo ◽  
Lakshmi S. Tallam ◽  
John V. Roberts ◽  
Elizabeth L. Brandon ◽  
John Biglane ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Injury ◽  
Salt Sensitivity ◽  
Metabolic Abnormalities ◽  
Salt Diet ◽  
Melanocortin 4 Receptor ◽  
Renal Structure ◽  
Long Term Impact ◽  
And Function

The purpose of this study was to determine the long-term impact of obesity and related metabolic abnormalities in the absence and presence of hypertension on renal injury and salt-sensitivity of blood pressure. Markers of renal injury and blood pressure salt sensitivity were assessed in 52- to 55-wk-old normotensive melanocortin-4 receptor-deficient (MC4R−/−) mice and lean C57BL/6J wild-type (WT) mice and in 22-wk-old MC4R−/− and WT mice made hypertensive by NG-nitro-l-arginine methyl ester (l-NAME) in the drinking water for 8 wk. Old MC4R−/− mice were 60% heavier, hyperinsulinemic, and hyperleptinemic but had similar mean arterial pressure (MAP) as WT mice (115 ± 2 and 117 ± 2 mmHg) on normal salt diet (0.4% NaCl). A high-salt diet (4.0% NaCl) for 12 days did not raise MAP in obese or lean mice [ΔMAP: MC4R (−/−) 4 ± 2 mmHg; WT, 2 ± 1 mmHg]. Obese MC4R−/− mice had 23% greater glomerular tuft area and moderately increased GFR compared with WT mice. Bowman's space, total glomerular area, mesangial matrix, urinary albumin excretion (UAE), renal TGF-β and collagen expression were not significantly different between old MC4R−/− and WT mice. Renal lipid content was greater but renal macrophage count was markedly lower in MC4R−/− than WT mice. Mild increases in MAP during l-NAME treatment (∼16 mmHg) caused small, but greater, elevations in UAE, renal TGF-β content, and macrophage infiltration in MC4R−/− compared with WT mice without significant changes in glomerular structure. Thus despite long-term obesity and multiple metabolic abnormalities, MC4R−/− mice have no evidence of renal injury or salt-sensitivity of blood pressure. These observations suggest that elevations in blood pressure may be necessary for obesity and related metabolic abnormalities to cause major renal injury or that MC4R−/− mice are protected from renal injury by mechanisms that are still unclear.

Salt sensitivity in hypertensive rats with angiotensin II administration

1990 ◽  
Vol 259 (5) ◽  
pp. R1012-R1016 ◽  
Author(s):  
K. Ando ◽  
Y. Sato ◽  
T. Fujita
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Salt Sensitivity ◽  
Ang Ii ◽  
Short Term ◽  
Salt Loading ◽  
Salt Diet ◽  
Dose Dependent Fashion ◽  
Dose Dependent

We examined the salt sensitivity of blood pressure in angiotensin II (ANG II)-induced hypertension. Wistar rats, salt loaded (0.66, 2, or 8% salt-containing diet) for 4 or 12 days, were infused intravenously with 15 or 60 ng/min of ANG II. Systolic blood pressure (SBP) was not increased by long-term (12 days) salt loading, and SBP was unchanged with ANG II and normal-salt (0.66%) diet. However, when combined with salt loading, ANG II produced hypertension in a dose-dependent fashion; compared with control (120 +/- 2 mmHg), SBP was increased with 15 ng/min of ANG II and 8% salt diet (145 +/- 5 mmHg, P less than 0.05) and with 60 ng/min of ANG II and either 2 or 8% salt diet (149 +/- 8 and 174 +/- 8 mmHg, P less than 0.05, respectively). Na space (exchangeable Na) was increased in a roughly similar pattern and correlated significantly (r = 0.531, P less than 0.05) with SBP. However, with 15 ng/min of ANG II, Na space was not different among rats on either level of salt loading, although the 8% salt diet elevated SBP. Data obtained with short-term (4 days) treatment indicate that an elevated Na space preceded development of hypertension. With 15 ng/min of ANG II and 8% salt diet for 4 days, Na space was markedly (P less than 0.05) increased, but SBP was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

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 Long-term low salt diet increases blood pressure by activation of the renin-angiotensin and sympathetic nervous systems

2018 ◽  
Vol 41 (8) ◽  
pp. 739-746
Author(s):  
Jialiang Wang ◽  
Yi Deng ◽  
Xue Zou ◽  
Hao Luo ◽  
Pedro A. Jose ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Salt Diet ◽  
Nervous Systems ◽  
Renin Angiotensin ◽  
Sympathetic Nervous Systems ◽  
Low Salt ◽  
Sympathetic Nervous

When Theatre was for All: the Cork Report, after Ten Years

1996 ◽  
Vol 12 (48) ◽  
pp. 367-383 ◽  
Author(s):  
Ian Brown ◽  
Rob Brannen
Keyword(s):  
Great Britain ◽  
Public Funding ◽  
Senior Lecturer ◽  
Healthy Development ◽  
The Arts ◽  
Art Form ◽  
Long Term Impact ◽  
And Function ◽  
Theatre Management

By the mid 'eighties, the Thatcher government's public funding restrictions had taken a firm hold, leading to a now familiar position of crisis theatre management. In 1985, under pressure from the profession, the Arts Council of Great Britain commissioned an independent enquiry, the first for sixteen years, to evaluate the needs of the publicly funded theatre and to determine funding priorities. Although the resulting Cork Enquiry was seen by many at the time as a cost-cutting exercise, eight months intensive research and evidence-taking led to a carefully constructed case for a funding increase against an estimated shortfall of up to £13.4 million – and also produced a broad vision of the nature of theatre in England. It is now ten years since the Cork Enquiry delivered its report, with the aim of ensuring the healthy development of an art form placed under severe financial constraint. Here lan Brown and Rob Brannen, Secretary and Assistant Secretary to the Enquiry, provide insight into the Enquiry's setting-up, its process, and formulation of recommendations. In the light of recent consultation exercises, they examine the nature and function of such reports alongside the long-term impact of the Cork Enquiry. lan Brown was Drama Director of the Arts Council of Great Britain from 1986 to 1994, and is now Professor and Head of the Drama Department at Queen Margaret College, Edinburgh. Rob Brannen is a Senior Lecturer in Drama at De Montfort University, Bedford.

Abstract 495: A Novel Test for Low Salt Sensitivity: Angiotensin type-II Receptor Recruitment After Dopamine-1 Receptor Stimulation in Urine-Derived Renal Proximal Tubule Cells

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
John J Gildea ◽  
Staci A Keene ◽  
Dylan T Lahiff ◽  
Robert E Van Sciver ◽  
Cynthia D Schoeffel ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Flow Cytometry ◽  
Clinical Study ◽  
Salt Sensitivity ◽  
High Salt ◽  
Salt Diet ◽  
Independent Events ◽  
Angiotensin Type 2 Receptor ◽  
Low Salt ◽  
Angiotensin Type

Salt-sensitivity of blood pressure is an inappropriate increase in blood pressure following high salt intake. Subjects in our clinical study were typed according to their salt-sensitivity status into 3 categories: High-Salt-Sensitive (HSS; ≥ 7 mmHg increase in mean arterial pressure (MAP) on a high salt diet of 300 mEq of sodium, 17% prevalence), Low-Salt-Sensitive (LSS:, who paradoxically showed a ≥ 7 mmHg increase in MAP on a low salt diet of 10 mEq of sodium, 11% prevalence), and Salt-Resistant (SR, individuals who showed no significant increase in blood pressure on either diet, 72% prevalence). We previously demonstrated that LSS subjects show increased recruitment of the natriuretic dopamine-1 receptor (D1R) to the plasma membrane following a salt stimulation as compared to HSS subjects. Stimulation of the D1R in RPTC with fenoldopam (dopaminergic agonist) results in recruitment of the natriuretic angiotensin type-2 receptor (AT2R) to the cell surface. We hypothesized that LSS individuals may also demonstrate an enhanced AT2R RPTC membrane recruitment compared to HSS individuals when challenged with fenoldopam. In order to gain access to fresh RPTC from each subject, we isolated exfoliated RPTC from randomly voided urine from SR, LSS, and HSS subjects from our clinical study. We measured three subjects from each category with a minimum of three voids for each subject. We counted individual cells as independent events using both the confocal microscope (n=245) and the flow cytometer (n=5344). We found an inverse correlation between AT2R recruitment and the degree of salt-sensitivity of blood pressure. Fenoldopam stimulated AT2R recruitment as measured by confocal microscopy (y = -0.0047x + 0.4966, R2 = 0.2488, P<0.0001) and flow cytometry (y =-0.057x + 1.5645, R2=0.2912, P=0.0185). Flow cytometry provided a more sensitive diagnostic for LSS than HSS subjects. AT2R recruitment was more predictive of LSS than HSS. AT2R recruitment may be used as a rapid method to test for LSS individuals who need to be identified and encouraged to increase their sodium intake in order to avoid paradoxical hypertension.

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 Long-Term Impact of Systolic Blood Pressure and Glycemia on the Development of Microalbuminuria in Essential Hypertension

Hypertension ◽  
2005 ◽  
Vol 45 (6) ◽  
pp. 1125-1130 ◽  
Author(s):  
Jose Maria Pascual ◽  
Enrique Rodilla ◽  
Carmen Gonzalez ◽  
Santiago Pérez-Hoyos ◽  
Josep Redon
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Systolic Blood Pressure ◽  
Long Term Impact
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