scholarly journals Impact of Mineralocorticoid Receptor And Angiotensin Ii Type 1 Receptor Antagonism on Blood Pressure Regulation in Obese Zucker Rats: Role of Sex Differences

2020 ◽  
Author(s):  
Jussara M do Carmo ◽  
Alexandre A da Silva ◽  
John E Hall
Keyword(s):  
Blood Pressure ◽  
Sex Differences ◽  
Mineralocorticoid Receptor ◽  
Combined Treatment ◽  
Zucker Rats ◽  
Male And Female ◽  
Obese Zucker Rats ◽  
Males And Females

Abstract Background Previous studies suggest that obesity-induced hypertension in females, but not males, is due to leptin-mediated stimulation of aldosterone secretion and subsequent activation of the mineralocorticoid receptor (MR). Although angiotensin II type 1 receptor (AT1R) antagonism lowers blood pressure (BP) in male obese Zucker rats (OZR), which have defective leptin signaling, the potential role of sex differences in BP responses to RAAS blockade, including MR antagonism, in obesity is still unclear. We tested the cardiovascular effects of MR antagonism, alone or in combination with AT1R blockade in male and female OZR (n=5/sex) and lean Zucker rats (LZR, n=7/sex). Methods BP and heart rate (HR) were measured by telemetry 24-hrs/day. After a 6-day control period, spironolactone (40 mg/kg/day) was given for 10 days followed by a 7-day combined treatment with losartan (20 mg/kg/day), and followed by 6-day post-treatment recovery period. Results Compared to lean rats, OZR were hypertensive (Mean arterial pressure: 115±4 vs. 104±2 and 111±s vs. 100±3 mmHg for males and females) and had lower HR (355±9 vs. 393±7 and 367±10 vs. 412±13 bpm). MR blockade alone did not alter BP or HR in lean or obese male and female Zucker rats, whereas combined treatment reduced BP in obese and lean rats by 31±3 vs. 21±1 and 8±1 vs. 5±1 mmHg in males and females, respectively. No changes were observed in HR. Conclusions These results suggest that there are important sex differences in BP responses to chronic AT1R blockade but no major involvement of MR activation in BP regulation in OZR.

scholarly journals Reduction of renal dopamine receptor expression in obese Zucker rats: role of sex and angiotensin II

2010 ◽  
Vol 299 (5) ◽  
pp. F1164-F1170 ◽  
Author(s):  
Xiaoyan Wang ◽  
Fengmin Li ◽  
Pedro A. Jose ◽  
Carolyn M. Ecelbarger
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Receptor Expression ◽  
Female Rats ◽  
Male Rats ◽  
Zucker Rats ◽  
Protein Levels ◽  
Obese Rats ◽  
Obese Zucker Rats

Dopamine produced by renal proximal tubules increases sodium excretion via a decrease in renal sodium reabsorption. Dopamine natriuresis is impaired in obese Zucker rats; however, the mechanism is not fully understood. To test the hypothesis that renal expression of one or more of the subtypes are altered in these rats, we measured whole kidney protein levels by immunoblotting of D1-like (D1R and D5R) and D2-like (D2R, D3R, and D4R) dopamine receptors in both male and female obese and lean Zucker rats. In obese males on 1% NaCl diet, D1R, D2R, D4R, and D5R were decreased, while D3R was increased, relative to lean rats. Under a 4% NaCl diet, D2R and D3R levels in obese rats were restored to lean levels. 4% NaCl diet reduced D5R in both body types, relative to 1% NaCl diet. Female rats had higher expression of D1R and D3R than did male; however, the sex difference for D1R was markedly blunted in obese rats. In obese rats, dietary candesartan (angiotensin II type 1 receptor blocker) normalized downregulated D1R and D2R, but either decreased (D3R), did not affect (D4R), or further downregulated (D5R) the other subtypes. Candesartan also decreased D4R in lean rats. In summary, reduced renal protein levels of D1R, D2R, D4R, and D5R in obese Zucker rats could induce salt sensitivity and elevate blood pressure. Increased angiotensin II type 1 receptor activity may be mechanistically involved in the decreased expression of D1R and D2R in obese rats. Finally, reduced D1R and D3R in male rats may contribute to sex differences in blood pressure.

scholarly journals Splenectomy decreases blood pressure and abolishes sex differences in renal Tregs in spontaneously hypertensive rats

2021 ◽  
Author(s):  
Ellen E Gillis ◽  
Kasey Belanger ◽  
Mahmoud Abdelbary ◽  
Riyaz Mohamed ◽  
Jingping Sun ◽  
...  
Keyword(s):  
Blood Pressure ◽  
T Cells ◽  
Sex Differences ◽  
Spontaneously Hypertensive Rats ◽  
Flow Cytometric Analysis ◽  
Hypertensive Rats ◽  
Male And Female ◽  
Spontaneously Hypertensive ◽  
Flow Cytometric

Over the past decade there has been increasing support for a role of the immune system in the development of hypertension. Our lab has previously reported that female spontaneously hypertensive rats (SHR) have a blood pressure (BP)-dependent increase in anti-inflammatory renal regulatory T cells (Tregs), corresponding to lower BP compared to males. However, little is known regarding the mechanism for greater renal Tregs in females. The current study was designed to test the hypothesis that the greater relative abundance of renal Tregs in female SHR is due to greater Treg production. To test this hypothesis, T cell profiles were measured in the spleen by flow cytometry in male and female SHR at 5 weeks and 14 weeks of age.  Splenic Tregs did not differ between males and females, suggesting sex differences in renal Tregs is not due to differences in production. To assess the role of the spleen in sex differences in renal Tregs and BP control, rats were randomized to receive sham surgery (CON) or splenectomy (SPLNX, n=6) at 12 wks of age and implanted with telemeters to measure BP. After 2 weeks, kidneys were harvested for flow cytometric analysis of T cells. Splenectomy increased BP in both sexes after 2 weeks. Renal Tregs decreased in both sexes after splenectomy, abolishing the sex differences in renal Tregs. In conclusion, splenic Tregs were comparable in male and female SHR, suggesting that sex differences in renal Tregs is due to differences in renal Treg recruitment, not Treg production.

scholarly journals Sex differences in renal mitochondrial function: a hormone-gous opportunity for research

2020 ◽  
Vol 319 (6) ◽  
pp. F1117-F1124
Author(s):  
Regina F. Sultanova ◽  
Ryan Schibalski ◽  
Irina A. Yankelevich ◽  
Krisztian Stadler ◽  
Daria V. Ilatovskaya
Keyword(s):  
Sex Differences ◽  
Reactive Oxygen Species Production ◽  
Mitochondrial Bioenergetics ◽  
Oxygen Species ◽  
Complex Interplay ◽  
Male And Female ◽  
Males And Females ◽  
Species Production ◽  
And Oxidative Stress

Sex differences (biological distinctions between males and females) present a complex interplay of genetic, developmental, biological, and environmental factors. More and more studies are shedding light on the importance of sex differences in normal physiology and susceptibility to cancer, cardiovascular and renal conditions, and neurodegenerative diseases. This mini-review is devoted to the role of sex dimorphisms in renal function, with a focus on the distinctions between male and female mitochondria. Here, we cover the aspects of renal mitochondrial bioenergetics where sex differences have been reported to date, for instance, biogenesis, reactive oxygen species production, and oxidative stress. Special attention is devoted to the effects of sex hormones, such as estrogen and testosterone, on mitochondrial bioenergetics in the kidney in physiology and pathophysiology.

Sex Differences in Renal Nitric Oxide Synthase, NAD(P)H Oxidase, and Blood Pressure in Obese Zucker Rats

2007 ◽  
Vol 4 (3) ◽  
pp. 214-229 ◽  
Author(s):  
Shahla Riazi ◽  
Veerendra K. Madala-Halagappa ◽  
Ana Paula Dantas ◽  
Xinqun Hu ◽  
Carolyn A. Ecelbarger
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Sex Differences ◽  
Nitric Oxide Synthase ◽  
Zucker Rats ◽  
Obese Zucker Rats ◽  
Oxide Synthase

scholarly journals Stem cell treatment improves post stroke neurological outcomes: a comparative study in male and female rats

2021 ◽  
pp. svn-2020-000834
Author(s):  
Koteswara Rao Nalamolu ◽  
Bharath Chelluboina ◽  
Casimir A Fornal ◽  
Siva Reddy Challa ◽  
David M Pinson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Sex Differences ◽  
Motor Function ◽  
Infarct Volume ◽  
Female Rats ◽  
Human Umbilical Cord ◽  
Male And Female ◽  
Post Stroke ◽  
Male And Female Rats ◽  
Males And Females

Background and purposeThe therapeutic potential of different stem cells for ischaemic stroke treatment is intriguing and somewhat controversial. Recent results from our laboratory have demonstrated the potential benefits of human umbilical cord blood-derived mesenchymal stem cells (MSC) in a rodent stroke model. We hypothesised that MSC treatment would effectively promote the recovery of sensory and motor function in both males and females, despite any apparent sex differences in post stroke brain injury.MethodsTransient focal cerebral ischaemia was induced in adult Sprague-Dawley rats by occlusion of the middle cerebral artery. Following the procedure, male and female rats of the untreated group were euthanised 1 day after reperfusion and their brains were used to estimate the resulting infarct volume and tissue swelling. Additional groups of stroke-induced male and female rats were treated with MSC or vehicle and were subsequently subjected to a battery of standard neurological/neurobehavioral tests (Modified Neurological Severity Score assessment, adhesive tape removal, beam walk and rotarod). The tests were administered at regular intervals (at days 1, 3, 5, 7 and 14) after reperfusion to determine the time course of neurological and functional recovery after stroke.ResultsThe infarct volume and extent of swelling of the ischaemic brain were similar in males and females. Despite similar pathological stroke lesions, the clinical manifestations of stroke were more pronounced in males than females, as indicated by the neurological scores and other tests. MSC treatment significantly improved the recovery of sensory and motor function in both sexes, and it demonstrated efficacy in both moderate stroke (females) and severe stroke (males).ConclusionsDespite sex differences in the severity of post stroke outcomes, MSC treatment promoted the recovery of sensory and motor function in male and female rats, suggesting that it may be a promising treatment for stroke.

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