scholarly journals Transgenic overexpression of glutathione S-transferase μ-type 1 reduces hypertension and oxidative stress in the stroke-prone spontaneously hypertensive rat

2019 ◽  
Vol 37 (5) ◽  
pp. 985-996 ◽  
Author(s):  
Erin Olson ◽  
Michal Pravenec ◽  
Vladimir Landa ◽  
H.H. Caline Koh-Tan ◽  
Anna F. Dominiczak ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spontaneously Hypertensive Rat ◽  
Glutathione S Transferase ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
And Oxidative Stress

scholarly journals Sex-specific computational models of the spontaneously hypertensive rat kidneys: factors affecting nitric oxide bioavailability

2017 ◽  
Vol 313 (2) ◽  
pp. F174-F183 ◽  
Author(s):  
Ying Chen ◽  
Jennifer C. Sullivan ◽  
Aurélie Edwards ◽  
Anita T. Layton
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Sex Differences ◽  
Computational Model ◽  
Solute Transport ◽  
Spontaneously Hypertensive Rat ◽  
Male And Female ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
And Oxidative Stress

The goals of this study were to 1) develop a computational model of solute transport and oxygenation in the kidney of the female spontaneously hypertensive rat (SHR), and 2) apply that model to investigate sex differences in nitric oxide (NO) levels in SHR and their effects on medullary oxygenation and oxidative stress. To accomplish these goals, we first measured NO synthase (NOS) 1 and NOS3 protein expression levels in total renal microvessels of male and female SHR. We found that the expression of both NOS1 and NOS3 is higher in the renal vasculature of females compared with males. To predict the implications of that finding on medullary oxygenation and oxidative stress levels, we developed a detailed computational model of the female SHR kidney. The model was based on a published male kidney model and represents solute transport and the biochemical reactions among O2, NO, and superoxide ([Formula: see text]) in the renal medulla. Model simulations conducted using both male and female SHR kidney models predicted significant radial gradients in interstitial fluid oxygen tension (Po2) and NO and [Formula: see text] concentration in the outer medulla and upper inner medulla. The models also predicted that increases in endothelial NO-generating capacity, even when limited to specific vascular segments, may substantially raise medullary NO and Po2 levels. Other potential sex differences in SHR, including [Formula: see text] production rate, are predicted to significantly impact oxidative stress levels, but effects on NO concentration and Po2 are limited.

scholarly journals Angiotensin II Type 1 Receptor Antagonist Downregulates Nonmuscle Myosin Heavy Chains in Spontaneously Hypertensive Rat Aorta

Hypertension ◽  
1999 ◽  
Vol 33 (4) ◽  
pp. 975-980 ◽  
Author(s):  
Kozo Fujii ◽  
Seiji Umemoto ◽  
Akihisa Fujii ◽  
Takahito Yonezawa ◽  
Toshihiro Sakumura ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Spontaneously Hypertensive Rat ◽  
Rat Aorta ◽  
Myosin Heavy Chains ◽  
Nonmuscle Myosin ◽  
Spontaneously Hypertensive ◽  
Heavy Chains ◽  
Hypertensive Rat

Abstract P160: Role of Uncoupling Protein 2 in Stroke Susceptibility of Stroke-prone Spontaneously Hypertensive Rat

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Speranza Rubattu ◽  
Maria Cotugno ◽  
Franca Bianchi ◽  
Sara Di Castro ◽  
Rosita Stanzione ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Expression ◽  
Mitochondrial Dysfunction ◽  
Spontaneously Hypertensive Rat ◽  
Uncoupling Protein ◽  
Uncoupling Protein 2 ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
Ucp2 Expression

Mitochondrial dysfunction causes severe cellular derangements potentially underlying tissue injury and consequent diseases. Evidence of a direct involvement of mitochondrial dysfunction in hypertensive target organ damage is still poor. The gene encoding Uncoupling Protein 2 (UCP2), a inner mitochondrial membrane protein, maps inside stroke QTL/STR1 in stroke prone spontaneously hypertensive rat (SHRSP). We explored the role of UCP2 in stroke pathogenesis of SHRSP. Male SHRSP, stroke resistant SHR (SHRSR) and reciprocal STR1/congenic rats were fed with stroke permissive Japanese style diet (JD). A group of SHRSP received JD plus fenofibrate (150 mg/kg/die). Rats were sacrificed at stroke occurrence. Additional SHRSR and SHRSP rats were sacrificed at 1, 3, 6, 12 months of age upon regular diet. SBP, BW, proteinuria, stroke signs were monitored. Brains were used for molecular analysis (UCP2 gene and protein expression, Nf-kB protein expression, oxidative stress quantification) and for histological analyses. As a result, brain UCP2 expression was reduced to 20% by JD only in SHRSP (showing 100% stroke occurrence by 7 weeks of JD). Fenofibrate protected SHRSP from stroke and upregulated brain UCP2 (+ 100%). Congenic rats carrying STR1/QTL showed increased (+100%) brain UCP2 expression, as compared to SHRSP, when resistant to stroke, and, viceversa, decreased (-50%) brain UCP2 levels, as compared to SHRSR, when susceptible to stroke. Brain UCP2 expression progressively decreased with aging only in SHRSP, down to 15% level at one year of age (when SHRSP showed spontaneous stroke). Both brain Nf-kB expression and oxidative stress levels increased when UCP2 expression was downregulated, and viceversa. Histological analysis showed both ischemic and haemorrhagic lesions at stroke occurrence. Our results highlight a role of UCP2 in stroke predisposition associated to hypertension in an animal model of complex human disease.

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