Sex-dependent hypertension and renal changes in aged rats with altered renal development

2014 ◽  
Vol 307 (4) ◽  
pp. F461-F470 ◽  
Author(s):  
Fara Saez ◽  
Virginia Reverte ◽  
Alexander Paliege ◽  
Juan Manuel Moreno ◽  
María T. Llinás ◽  
...  

Numerous studies have evaluated blood pressure (BP) and renal changes in several models of developmental programming of hypertension. The present study examined to what extent BP, renal hemodynamic, and renal structure are affected at an old age in male and female animals with altered renal development. It also evaluated whether renal damage is associated with changes in cyclooxygenase (COX)-2 and neuronal nitric oxide synthase (NOS1) expression and immunoreactivity. Experiments were carried out in rats at 10–11 and 16–17 mo of age treated with vehicle or an ANG II type 1 receptor antagonist during the nephrogenic period (ARAnp). A progressive increment in BP and a deterioration of renal hemodynamics were found in both sexes of ARAnp-treated rats, with these changes being greater ( P < 0.05) in male rats. The decrease in glomerular filtration rate at the oldest age was greater ( P < 0.05) in male (74%) than female (32%) ARAnp-treated rats. Sex-dependent deterioration of renal structure was demonstrated in optical and electron microscopic experiments. COX-2 and NOS1 immunoreactivity were enhanced in the macula densa of male but not female ARAnp-treated rats. The present study reports novel findings suggesting that stimuli that induce a decrease of ANG II effects during renal development lead to a progressive increment in BP and renal damage at an old age in both sexes, but these BP and renal changes are greater in males than in females. The renal damage is associated with an increase of COX-2 and NOS1 in the macula densa of males but not females with altered renal development.

2004 ◽  
Vol 286 (5) ◽  
pp. F945-F954 ◽  
Author(s):  
Anderson Ricardo Roman Gonçalves ◽  
Clarice Kazue Fujihara ◽  
Ana Lúcia Mattar ◽  
Denise Maria Avancini Costa Malheiros ◽  
I. L. Noronha ◽  
...  

Chronic renal injury can be mediated by angiotensin II (ANG II) and prostanoids through hemodynamic and inflammatory mechanisms and attenuated by individual suppression of these mediators. In rats with ⅚ renal ablation (Nx), we investigated 1) the intrarenal distribution of COX-2, ANG II, and the AT1 receptor (AT1R); 2) the renoprotective and antiinflammatory effects of an association between the AT1R blocker, losartan (Los), and the gastric sparing anti-inflammatory nitroflurbiprofen (NOF). Adult male Munich-Wistar rats underwent Nx or sham operation (S), remaining untreated for 30 days, after which renal structure was examined in 12 Nx rats (Nxpre). The remaining rats were followed during an additional 90 days, distributed among 4 treatment groups: NxV (vehicle), NxLos (Los), NxNOF (NOF), and NxLos/NOF (Los/NOF). Nxpre rats exhibited marked albuminuria, hypertension, glomerulosclerosis, interstitial expansion, and macrophage infiltration, accompanied by abnormal glomerular, vascular, and interstitial COX-2 expression. ANG II appeared in interstitial cells, in contrast to S, in which ANG II was virtually confined to afferent arterioles. Intrarenal AT1R distribution shifted from mostly tubular in S to predominantly interstitial in Nxpre. All these changes were aggravated at 120 days and attenuated by Los and NOF monotherapies. Los/NOF treatment arrested renal structural injury and ANG II expression and reversed hypertension, albuminuria, and renal inflammation. In conclusion, abnormal expression of COX-2, ANG II, and AT1R may be key to development of renal injury in Nx. Concomitant COX-2 inhibition and AT1R blockade arrested renal injury and may represent a useful strategy in the treatment of chronic nephropathies.


2020 ◽  
Vol 1 (1) ◽  
pp. 39-50
Author(s):  
Al-Sayeda A. Newairy ◽  
◽  
Fatma A. Hamaad ◽  
Mayssaa M. Wahby ◽  
Heba M. Abdou ◽  
...  

Monosodium glutamate (MSG) is a flavor enhancer. Oxidative neurotoxicity of MSG is well established. This study explored the therapeutic effect of red clover’s (RC) extract against MSG–induced neurodegeneration. HPLC-analysis revealed that formononetin, genistein, daidzein and biochanin A are the major isoflavones in RC’s extract. Four equal groups of male rats were used: control group, MSG-treated group, MSG plus RC-treated group and RC-treated group. The gene expression of iNOS, TNF-α, Cox-2 and p53 were evaluated in the brain extract using RT-PCR. The histological and electron microscopic examinations as well as the cholinergic function, the neurotransmitters and the oxidative status were also assessed. The MSG significantly up regulated the expression levels of iNOS, TNF-α, Cox-2 and p53. The activity of acetyl cholinesterase (AChE), the monoamine neurotransmitters and the oxidative status as well as the histological and electron microscopic examinations confirmed the MSG-induced neurodegeneration. The administration of RC plus MSG diminished the expression of the inflammatory cytokines, the activity of AChE and the levels of monoamine neurotransmitters. RC also ameliorated the oxidative stress and the histological and the electron microscopic alterations. Accordingly, the present study provides an insight on the antioxidative and anti-inflammatory potentials of RC’s extract as neuroprotective agent.


2013 ◽  
Vol 304 (1) ◽  
pp. F33-F40 ◽  
Author(s):  
Virginia Reverte ◽  
Antonio Tapia ◽  
Goretti Baile ◽  
Juan Gambini ◽  
Ignacio Gíménez ◽  
...  

Numerous studies have demonstrated that angiotensin II (ANG II) is involved in hypertension and renal changes occurring as a consequence of an adverse event during renal development. However, it was unknown whether this involvement is sex and age dependent. This study examines whether the increments in arterial pressure (AP) and in the renal sensitivity to ANG II are sex and age dependent in rats with altered renal development. It also evaluates whether the ANG II effects are accompanied by increments in AT1 receptors and oxidative stress. Experiments were performed in 3- to 4- and 10- to 11-mo-old rats treated with vehicle or an AT1 receptor antagonist (ARAnp) during the nephrogenic period. ARAnp-treated rats were hypertensive, but an age-dependent rise in AP was only found in males. Three days of treatment with candesartan (7 mg·kg−1·day−1) led to a fall of AP that was greater ( P < 0.05) in male than in female 10- to 11-mo-old ARAnp-treated rats. Oxidated proteins were elevated ( P < 0.05), and the decrease in AP elicited by candesartan was reduced ( P < 0.05) when these rats are also treated with tempol (18 mg·kg−1·day−1). Hypertension was not maintained by an elevation of AT1 receptors in kidneys and mesenteric arteries. The acute renal hemodynamic response to ANG II (30 ng·kg−1·min−1) was similarly enhanced ( P < 0.05) in both sexes of ARAnp-treated rats at 3–4 but not at 10–11 mo of age. Our results suggest that an adverse event during the nephrogenic period induces an ANG II-dependent increment in AP that is aggravated only in males during aging and that oxidative stress but not an increase in AT1 receptor contributes to the rise in AP. This study also shows that the renal hemodynamic sensitivity to ANG II is transitorily enhanced in both sexes of rats with altered renal development.


2007 ◽  
Vol 293 (2) ◽  
pp. R695-R700 ◽  
Author(s):  
Analia Loria ◽  
Virginia Reverte ◽  
Francisco Salazar ◽  
Fara Saez ◽  
M. Teresa Llinas ◽  
...  

The aim was to evaluate whether blockade of ANG II effects during renal development modifies the renal response to an increment of plasma amino acid concentration. It was also examined in anesthetized rats whether the reduction of the renal ability to eliminate an acute volume expansion (VE), elicited by blockade of ANG II during renal development, is sex and/or age dependent. Newborn Sprague-Dawley rats were treated with vehicle or an AT1-receptor antagonist (ARA) during postnatal nephrogenesis. Amino acid infusion induced increments ( P < 0.05) of glomerular filtration rate (31 ± 6%) and renal plasma flow (26 ± 5%) in male but not in female vehicle-treated rats. Natriuretic and diuretic responses to amino acid infusion were similar in male and female vehicle-treated rats. These renal hemodynamics and excretory responses to amino acid infusion were abolished in ARA-treated rats. Renal responses to VE were evaluated at 3–4 and 9–10 mo of age in vehicle and ARA-treated rats. VE-induced natriuresis and diuresis were reduced by more than 38% ( P < 0.05) in 3- to 4-mo-old male and female ARA-treated rats. An age-dependent reduction ( P < 0.05) in the renal ability to eliminate VE was found in male but not in female rats treated with ARA. Our results demonstrate that the renal effects induced by an increment in amino acids are abolished when ANG II effects have been reduced during nephrogenesis. In addition, this reduction of ANG II effects elicits an impairment of the renal ability to eliminate an acute VE in males and females, which is aggravated by age only in male rats.


Author(s):  
Aline Byrnes ◽  
Elsa E. Ramos ◽  
Minoru Suzuki ◽  
E.D. Mayfield

Renal hypertrophy was induced in 100 g male rats by the injection of 250 mg folic acid (FA) dissolved in 0.3 M NaHCO3/kg body weight (i.v.). Preliminary studies of the biochemical alterations in ribonucleic acid (RNA) metabolism of the renal tissue have been reported recently (1). They are: RNA content and concentration, orotic acid-c14 incorporation into RNA and acid soluble nucleotide pool, intracellular localization of the newly synthesized RNA, and the specific activity of enzymes of the de novo pyrimidine biosynthesis pathway. The present report describes the light and electron microscopic observations in these animals. For light microscopy, kidney slices were fixed in formalin, embedded, sectioned, and stained with H & E and PAS.


Author(s):  
Venita F. Allison

In 1930, Moore, Hughes and Gallager reported that after castration seminal vesicle epithelial cell atrophy occurred and that cell regeneration could be achieved with daily injections of testis extract. Electron microscopic studies have confirmed those observations and have shown that testosterone injections restore the epithelium of the seminal vesicle in adult castrated male rats. Studies concerned with the metabolism of androgens point out that dihydrotestosterone stimulates cell proliferation and that other metabolites of testosterone probably influence secretory function in certain target cells.Although the influence of androgens on adult seminal vesicle epithelial cytology is well documented, little is known of the effect of androgen depletion and replacement on those cells in aging animals. The present study is concerned with the effect of castration and testosterone injection on the epithelium of the seminal vesicle of aging rats.


Author(s):  
D.R. Mattie ◽  
C.J. Hixson

Dimethylmethylphosphonate (DMMP) is a simple organophosphate used industrially as a flame retardant and to lower viscosity in polyester and epoxy resins. The military considered the use of DMMP as a nerve gas simulant. Since military use of DMMP involved exposure by inhalation, there was a need for a subchronic inhalation exposure to DMMP to fully investigate its toxic potential.Male Fischer-344 rats were exposed to 25 ppm or 250 ppm DMMP vapor on a continuous basis for 90 days. An equal number of control rats were sham-exposed. Following the 90-day continuous exposure period, 15 male rats were sacrificed from each group. Two rats from each group had the left kidney perfused for electron microscopic examination. The kidneys were perfused from a height of 150 cm water with 1% glutaraldehyde in Sorensen's 0.1M phosphate buffer pH 7.2. An additional kidney was taken from a rat in each group and fixed by immersion in 2.5% glutaraldehyde and 2% paraformaldehyde in 0.1M cacodylate buffer pH 7.4. A portion of the 9 kidneys collected for electron microscopy were processed into Epon 812. Thin sections, stained with uranyl acetate and lead citrate, were examined with a JEOL 100B Transmission Electron Microscope. Microvilli height was measured on photographs of the cells of proximal tubules. This data, along with morphologic features of the cells, allows the proximal convoluted tubules (PCT) to be identified as being S1, S2, or S3 segment PCT.


Author(s):  
O. M. Faroon ◽  
R. W. Henry ◽  
M. G. Soni ◽  
H. M. Mehendale

Previous work has shown that mirex undergoes photolytic dechlorination to chlordecone (CD) (KeponeR) in the environment. Much work has shown that prior exposure to nontoxic levels of CD causes potentiation of hepatotoxicity and lethality of CCl4, BrCCl3 and other halomethane compounds. Potentiation of bromotrichloromethane hepatotoxicity has been associated with compounds that stimulate the activity of hepatic mixed-function oxidase (MFO). An increase in the metabolism of halomethane by the MFO to a free radical initiates peroxidative decomposition of membranal lipids ending in massive cellular injury. However, not all MFO inducers potentiate BrCCl3 hepatotoxicity. Potentiation by much larger doses of phenobarbital is minimal and th at by a more potent inducer of MFO, mirex, is negligible at low doses. We suggest that the CD and bromotrichloromethane interaction results in a depletion of cellular energy and thereby reducing the cellular ability to undergo mitosis.


2021 ◽  
Vol 22 (7) ◽  
pp. 3762
Author(s):  
Sarah M. Kedziora ◽  
Kristin Kräker ◽  
Lajos Markó ◽  
Julia Binder ◽  
Meryam Sugulle ◽  
...  

Preeclampsia (PE) is characterized by the onset of hypertension (≥140/90 mmHg) and presence of proteinuria (>300 mg/L/24 h urine) or other maternal organ dysfunctions. During human PE, renal injuries have been observed. Some studies suggest that women with PE diagnosis have an increased risk to develop renal diseases later in life. However, in human studies PE as a single cause of this development cannot be investigated. Here, we aimed to investigate the effect of PE on postpartum renal damage in an established transgenic PE rat model. Female rats harboring the human-angiotensinogen gene develop a preeclamptic phenotype after mating with male rats harboring the human-renin gene, but are normotensive before and after pregnancy. During pregnancy PE rats developed mild tubular and glomerular changes assessed by histologic analysis, increased gene expression of renal damage markers such as kidney injury marker 1 and connective-tissue growth factor, and albuminuria compared to female wild-type rats (WT). However, four weeks postpartum, most PE-related renal pathologies were absent, including albuminuria and elevated biomarker expression. Only mild enlargement of the glomerular tuft could be detected. Overall, the glomerular and tubular function were affected during pregnancy in the transgenic PE rat. However, almost all these pathologies observed during PE recovered postpartum.


Author(s):  
Lajos Markó ◽  
Joon-Keun Park ◽  
Norbert Henke ◽  
Song Rong ◽  
András Balogh ◽  
...  

Abstract Aims B-cell lymphoma/leukaemia 10 (Bcl10) is a member of the CARMA-Bcl10-MALT1 signalosome, linking angiotensin (Ang) II, and antigen-dependent immune-cell activation to nuclear factor kappa-B signalling. We showed earlier that Bcl10 plays a role in Ang II-induced cardiac fibrosis and remodelling, independent of blood pressure. We now investigated the role of Bcl10 in Ang II-induced renal damage. Methods and results Bcl10 knockout mice (Bcl10 KO) and wild-type (WT) controls were given 1% NaCl in the drinking water and Ang II (1.44 mg/kg/day) for 14 days. Additionally, Bcl10 KO or WT kidneys were transplanted onto WT mice that were challenged by the same protocol for 7 days. Kidneys of Ang II-treated Bcl10 KO mice developed less fibrosis and showed fewer infiltrating cells. Nevertheless, neutrophil gelatinase-associated lipocalin (Ngal) and kidney injury molecule (Kim)1 expression was higher in the kidneys of Ang II-treated Bcl10 KO mice, indicating exacerbated tubular damage. Furthermore, albuminuria was significantly higher in Ang II-treated Bcl10 KO mice accompanied by reduced glomerular nephrin expression and podocyte number. Ang II-treated WT mice transplanted with Bcl10 KO kidney showed more albuminuria and renal Ngal, compared to WT- > WT kidney-transplanted mice, as well as lower podocyte number but similar fibrosis and cell infiltration. Interestingly, mice lacking Bcl10 in the kidney exhibited less Ang II-induced cardiac hypertrophy than controls. Conclusion Bcl10 has multi-faceted actions in Ang II-induced renal damage. On the one hand, global Bcl10 deficiency ameliorates renal fibrosis and cell infiltration; on the other hand, lack of renal Bcl10 aggravates albuminuria and podocyte damage. These data suggest that Bcl10 maintains podocyte integrity and renal function.


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