Effects of Dietary Salt Load and Salt Depletion on the Course of Hypertension and Angiotensin II Levels in Male and Female Heterozygous Ren-2 Transgenic Rats

Background. Angiotensin-converting enzyme 2/angiotensin (1-7)/Mas receptor (ACE2/Ang-1-7/MasR) appears to counteract most of the deleterious actions of angiotensin-converting enzyme/angiotensin II/angiotensin II receptor 1 (ACE/Ang II/AT1R) in renal ischemia/reperfusion (I/R) injury but ACE2 activity and its levels are sexually dimorphic in the kidney. This study was designed to evaluate the effects of activation endogenous ACE2 using the diminazene aceturate (DIZE) in renal I/R injury in male and female rats.Methods. 36 Wistar rats were divided into two groups of male and female and each group distinct to three subgroups (n=6). I/R group was subjected to 45 min of bilateral ischemia and 24 h of reperfusion, while treatment group received DIZE (15 mg/kg/day) for three days before the induction of I/R. The other group was assigned as the sham-operated group.Results. DIZE treatment in male rats caused a significant decrease in blood urea nitrogen (BUN), creatinine, liver functional indices, serum malondialdehyde (MDA), and increase kidney nitrite levels (P<0.05), and in female rats a significant increase in creatinine and decrease serum nitrite levels compared to the I/R group (P<0.05).Conclusions. DIZE may protect the male kidney from renal I/RI through antioxidant activity and elevation of circulating nitrite level.

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Renin and prorenin have no direct effect on aldosterone synthesis in the human adrenocortical cell lines H295R and HAC15

Journal of the Renin-Angiotensin-Aldosterone System ◽

10.1177/1470320312438792 ◽

2012 ◽

Vol 13 (3) ◽

pp. 360-366 ◽

Cited By ~ 9

Author(s):

Pieter M Jansen ◽

Johannes Hofland ◽

Anton H van den Meiracker ◽

Frank H de Jong ◽

AH Jan Danser

Keyword(s):

Angiotensin Ii ◽

Cell Lines ◽

Renin Angiotensin System ◽

Adrenocortical Cell ◽

Transgenic Rats ◽

Angiotensin System ◽

Extracellular Signal Regulated Kinase ◽

Erk Phosphorylation ◽

Extracellular Signal ◽

Aldosterone Production

Introduction: Transgenic rats expressing the human (pro)renin receptor (h(P)RR) have elevated plasma aldosterone levels despite unaltered levels, in plasma and adrenal, of renin and angiotensin II. Materials and methods: To investigate whether renin/prorenin–(P)RR interaction underlies these elevated aldosterone levels, the effect of (pro)renin on steroidogenesis was compared with that of angiotensin II in two (P)RR-expressing human adrenocortical cell lines, H295R and HAC15. Angiotensin II rapidly induced extracellular signal-regulated kinase (ERK) phosphorylation and increased the expression of STAR, CYP21A2, CYP11B2, and CYP17A1 at 6 and 24 hours, whereas the expression of CYP11A1 and HSD3B2 remained unaltered. Incubation with renin or prorenin at nanomolar concentrations had no effect on the expression of any of the steroidogenic enzymes tested, nor resulted in ERK phosphorylation. Angiotensin II, but not renin or prorenin, induced aldosterone production. Conclusion: Although the (P)RR is present in adrenocortical cells, renin and prorenin do not elicit ERK phosphorylation nor directly affect steroid production via this receptor at nanomolar concentrations. Thus, direct (pro)renin–(P)RR interaction is unlikely to contribute to the elevated aldosterone levels in human (P)RR transgenic rats. This conclusion also implies that the aldosterone rise that often occurs during prolonged renin–angiotensin system blockade is rather due to the angiotensin II ‘escape’ during such blockade.

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Effect of sympathetic and angiotensin-aldosterone systems on renal salt conservation in the rat

AJP Renal Physiology ◽

10.1152/ajprenal.1997.272.4.f538 ◽

1997 ◽

Vol 272 (4) ◽

pp. F538-F544 ◽

Cited By ~ 2

Author(s):

U. Honrath ◽

A. T. Veress ◽

C. K. Chong ◽

H. Sonnenberg

Keyword(s):

Control Group ◽

Dietary Salt ◽

Drug Induced ◽

Efferent Nerve ◽

Salt Diet ◽

Salt Excretion ◽

Losartan Group ◽

Chloride Excretion ◽

Salt Depletion ◽

6 Hydroxydopamine

During dietary salt deprivation, the sympathetic nervous system and the angiotensin-aldosterone system are stimulated. Both systems are thought to be essential for maximal salt conservation by the kidney. To study their relative contributions, we produced negative salt balance in rats by intraperitoneal injection of furosemide, followed by a low-salt diet (<0.008% NaCl). In a 1-wk metabolic study, the animals were unable to replace the drug-induced salt deficit. Six groups of rats were studied. A control group established baseline function, a second group of 6-hydroxydopamine (OHDA) rats were treated with OHDA to destroy sympathetic efferent nerve terminals, and a third group (losartan) were treated with the angiotensin-receptor antagonist losartan. The influence of catecholamines and aldosterone released from the adrenal gland was studied in a further three groups. Rats were sham-adrenalectomized (sham), subjected to bilateral adrenal enucleation (Enuc) to eliminate catecholamine secretion, or were bilaterally adrenalectomized (Adx), eliminating both catecholamine and corticosteroid release. Dexamethasone was used as glucocorticoid replacement in this group. Steady-state urinary salt excretion was not different between control and OHDA rats. The losartan group showed significantly increased sodium but not chloride excretion. Surprisingly, there were no differences in salt excretion among sham, Enuc, and Adx groups. We conclude that, during a state of chronic salt depletion, renal mechanism(s) independent of neuronally released or systemically circulating catecholamines or of adrenally released aldosterone can ensure maximal salt conservation by the kidney. Although our data show that losartan increased sodium excretion under these conditions, we suggest that the losartan effect can be explained by a reduction of bicarbonate reabsorption, obligating simultaneous excretion of the cation.

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Effects of Angiotensin II and Dietary Salt on Neurogenic Vasomotor Tone: Dose Dependancy

The FASEB Journal ◽

10.1096/fasebj.20.4.a754-b ◽

2006 ◽

Vol 20 (4) ◽

Author(s):

Fiona Dianne McBryde ◽

Carolyn J Barrett ◽

Sarah‐Jane Guild ◽

Simon C Malpas

Keyword(s):

Angiotensin Ii ◽

Dietary Salt ◽

Vasomotor Tone

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Urinary excretion of angiotensinogen in male and female Sprague Dawley rats during angiotensin II infusion and high salt diet

The FASEB Journal ◽

10.1096/fasebj.24.1_supplement.1024.28 ◽

2010 ◽

Vol 24 (S1) ◽

Author(s):

Vicky F. Rands ◽

Charlene Byrd ◽

Dale Seth ◽

Hiroyuki Kobori ◽

Minolfa C Prieto

Keyword(s):

Angiotensin Ii ◽

Urinary Excretion ◽

High Salt ◽

Sprague Dawley ◽

High Salt Diet ◽

Salt Diet ◽

Male And Female ◽

Sprague Dawley Rats

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Cardiac-Specific Overexpression of Angiotensin II Type 1 Receptor in Transgenic Rats

Molecular Cardiology - Methods in Molecular Medicine ◽

10.1385/1-59259-879-x:389 ◽

2005 ◽

pp. 389-403 ◽

Cited By ~ 1

Author(s):

Sigrid Hoffmann

Keyword(s):

Angiotensin Ii ◽

Transgenic Rats

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Abstract 7: Angiotensin II Type 2 Receptor Deficiency Increases Renal ACE/ACE2 Ratio-Ang II-AT1R Expression In Male but not in Female Mice

Hypertension ◽

10.1161/hyp.60.suppl_1.a7 ◽

2012 ◽

Vol 60 (suppl_1) ◽

Author(s):

Quaisar Ali ◽

Yonnie Wu ◽

Tadashi Inagami ◽

Tahir Hussain

Keyword(s):

Blood Pressure ◽

Renal Function ◽

Angiotensin Ii ◽

Renin Activity ◽

Ang Ii ◽

Male And Female ◽

Female Mice ◽

Gender Specific

Angiotensin II acting via Angiotensin II type 2 receptors (AT2Rs) is believed to be protective against blood pressure increase and affects renal function under pathophysiological condition. Recently we have observed that stimulation of AT2Rs in male obese Zucker rats has shifted the two opposing arms of renin angiotensin system (RAS) i.e. ACE-Ang II-AT1 vs ACE2/Ang-(1-7)-Mas. Evidence suggests that estrogen regulates RAS, including AT2R in female mice. We hypothesized that AT2R has a gender specific regulation of RAS. In the present study, we investigated the role of AT2Rs in regulating RAS components in male and female mice. Kidney cortex from AT2R knockout (AT2RKO) male and female mice and wild type (WT) with similar background (C57BL/6) of 20 weeks of age were used in the study. The cortical ACE expression (ng ACE/μg tissue) was significantly increased in AT2RKO mice (3±0.02) compared to WT males (1.9±0.02). LC/MS analysis of cortical tissue revealed that Ang II was also significantly increased in AT2RKO mice (WT: 31±3, AT2RKO: 47±3 fmoles/mg tissue). Deletion of AT2R significantly increased AT1R (204%, 204 of 100) expression and had no effect on renin activity compared to WT males. The cortical expression of ACE2 activity (WT: 113±8, AT2RKO: 40±11, RFU/min), Ang-(1-7) levels (WT: 7.3±1.4, AT2RKO: 3±0.8 fmoles/mg tissue) and Mas receptor (AT2RKO: 54±15, % of WT) was significantly decreased in AT2RKO males compared to WT. The cortical expression of the AT2R and MasR was 2-fold greater in WT females compared to WT male. The renin activity (WT: 32±2, AT2RKO: 21±0.3, RFU/min) and MasR expression (WT: 187.5±55, AT2KO: 47±9) was significantly decreased in AT2RKO females compared to the female WT. Interestingly, Ang-(1-7) level (WT: 5.7±0.7, AT2RKO 2.6±0.7 fmoles/mg tissue) was decreased but no changes in ACE or ACE2 activity was observed in AT2KO females compared to their WT, suggesting a role of non-ACE2 pathway. This study suggests that AT2R regulates ACE/ACE2 ratio-Ang II-AT1R expression negatively only in males, whereas in females, it regulates Ang-(1-7) potentially via non-ACE2 pathway. Such changes indicate a gender specific mechanisms potentially associated with AT2R-mediated regulation of renal function and blood pressure control.

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In vitro production of angiotensin II by isolated glomeruli

AJP Renal Physiology ◽

10.1152/ajprenal.1995.268.2.f266 ◽

1995 ◽

Vol 268 (2) ◽

pp. F266-F272 ◽

Cited By ~ 5

Author(s):

B. A. Atiyeh ◽

B. S. Arant ◽

W. L. Henrich ◽

M. G. Seikaly

Keyword(s):

Angiotensin Ii ◽

Incubation Medium ◽

Renin Angiotensin System ◽

Ang Ii ◽

In Vitro Production ◽

Vascular Control ◽

Isolated Glomeruli ◽

Salt Depletion ◽

Wistar Kyoto

The glomerulus has several components of the renin-angiotensin system (RAS). The purpose of this study was to evaluate the ability of glomeruli isolated from adult Wistar-Kyoto rats to produce angiotensin II (ANG II). When isolated glomeruli were incubated in Krebs buffer, the peak concentration of immunoreactive angiotensin (ANG) in the incubation medium, representing simultaneous production and degradation, occurred after 15 min of incubation (3.98 +/- 0.34 pg.mg protein-1.15 min-1, of which 18% was ANG II. When 125I-labeled ANG II was incubated with isolated glomeruli, the half-life of ANG II was 6.06 min. Hence, we estimated ANG II production at 3.77 +/- 0.21 pg.mg protein-1.15 min-1. When angiotensinogen-rich serum was added to the incubation medium, ANG concentration at 15 min increased by 500-fold (1,978 +/- 44 pg.mg protein-1.15 min-1, P < 0.001). ANG concentration in the glomerular incubate responded to perturbations known to alter systemic RAS. Enalaprilat, chymostatin, propranolol, and renin antiserum decreased ANG concentration in glomerular incubate, whereas salt depletion increased this (P < 0.05). We conclude that the rat glomerulus can generate ANG II independent of neural, hormonal, or vascular control.

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