scholarly journals Oxidative stress induces BH4 deficiency in male, but not female, SHR

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Ellen E. Gillis ◽  
Krystal N. Brinson ◽  
Olga Rafikova ◽  
Wei Chen ◽  
Jacqueline B. Musall ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spontaneously Hypertensive Rats ◽  
No Synthase ◽  
Hypertensive Rats ◽  
Male And Female ◽  
Spontaneously Hypertensive ◽  
No Bioavailability ◽  
Renal Inner Medulla ◽  
Relative Deficiency ◽  
To Receive

We previously published that female spontaneously hypertensive rats (SHR) have significantly greater nitric oxide (NO) bioavailability and NO synthase (NOS) enzymatic activity in the renal inner medulla (IM) compared with age-matched males, although the mechanism responsible remains unknown. Tetrahydrobiopterin (BH4) is a critical cofactor required for NO generation, and decreases in BH4 as a result of increases in oxidative stress have been implicated in the pathogenesis of hypertension. As male SHR are known to have higher levels of oxidative stress compared with female SHR, we hypothesized that relative BH4 deficiency induced by oxidative stress in male SHR results in lower levels of NOS activity in renal IM compared with females. Twelve-week-old male and female SHR were randomized to receive tempol (30 mg/kg/day via drinking water) or vehicle for 2 weeks. Tempol treatment did not affect blood pressure (BP) in either sex, but reduced peroxynitrite levels only in males. Females had more total biopterin, dihydrobiopterin (BH2), and BH4 levels in renal IMs than males, and tempol treatment eliminated these sex differences. Females had greater total NOS activity in the renal IM than males, and adding exogenous BH4 to the assay increased NOS activity in both sexes. This sex difference in total NOS and the effect of exogenous BH4 were abolished with tempol treatment. We conclude that higher oxidative stress in male SHR results in a relative deficiency of BH4 compared with females, resulting in diminished renal NOS activity in the male.

scholarly journals Renal NOS activity, expression, and localization in male and female spontaneously hypertensive rats

2010 ◽  
Vol 298 (1) ◽  
pp. R61-R69 ◽  
Author(s):  
Jennifer C. Sullivan ◽  
Jennifer L. Pardieck ◽  
Kelly A. Hyndman ◽  
Jennifer S. Pollock
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Renal Cortex ◽  
No Production ◽  
Hypertensive Rats ◽  
Male And Female ◽  
Spontaneously Hypertensive ◽  
The Status ◽  
No Bioavailability ◽  
Males And Females ◽  
Renal Inner Medulla

The goal of this study was to examine the status of the renal nitric oxide (NO) system by determining NO synthase (NOS) isoform activity and expression within the three regions of the kidney in 14-wk-old male and female spontaneously hypertensive rats (SHR). NOS activity, and NOS1 and NOS3 protein expressions and localization were comparable in the renal cortex and outer medulla of male and female SHR. In contrast, male SHR had significantly less NOS1 and NOS3 enzymatic activity (0 ± 5 and 53 ± 7 pmol·mg−1·30 min−1, respectively) compared with female SHR (37 ± 16 and 172 ± 40 pmol·mg−1·30 min−1, respectively). Lower levels of inner medullary NOS1 activity in male SHR were associated with less NOS1 protein expression [45 ± 7 relative densitometric units (RDU)] and fewer NOS1-positive cells in the renal inner medulla compared with female SHR (79 ± 12 RDU). Phosphorylation of NOS3 is an important determinant of NOS activity. Male SHR had significantly greater phosphorylation of NOS3 on threonine 495 in the renal cortex compared with females (0.25 ± 0.05 vs. 0.15 ± 0.06 RDU). NOS3 phosphorylation was comparable in males and females in the other regions of the kidney. cGMP levels were measured as an indirect index of NO production. cGMP levels were significantly lower in the renal cortex (0.08 ± 0.01 pmol/mg) and inner medulla (0.43 ± 0.02 pmol/mg) of male SHR compared with females (cortex: 0.14 ± 0.02 pmol/mg; inner medulla: 0.56 ± 0.02 pmol/mg). Our data suggest that the effect of the sex of the animal on NOS activity and expression is different in the three regions of the SHR kidney and supports the hypothesis that male SHR have lower NO bioavailability compared with females.

Exercise training improves aortic endothelium-dependent vasorelaxation and determinants of nitric oxide bioavailability in spontaneously hypertensive rats

2004 ◽  
Vol 96 (6) ◽  
pp. 2088-2096 ◽  
Author(s):  
Drew A. Graham ◽  
James W. E. Rush
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Exercise Training ◽  
Spontaneously Hypertensive Rats ◽  
No Synthase ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Protein Levels ◽  
Endothelial No Synthase ◽  
Endothelium Dependent Relaxation

The present study examined in vitro vasomotor function and expression of enzymes controlling nitric oxide (NO) bioavailability in thoracic aorta of adult male normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) that either remained sedentary (Sed) or performed 6 wk of moderate aerobic exercise training (Ex). Training efficacy was confirmed by elevated maximal activities of both citrate synthase ( P = 0.0024) and β-hydroxyacyl-CoA dehydrogenase ( P = 0.0073) in the white gastrocnemius skeletal muscle of Ex vs. Sed rats. Systolic blood pressure was elevated in SHR vs. WKY ( P < 0.0001) but was not affected by Ex. Despite enhanced endothelium-dependent relaxation to 10-8 M ACh in SHR vs. WKY ( P = 0.0061), maximal endothelium-dependent relaxation to 10-4 M ACh was blunted in Sed SHR (48 ± 12%) vs. Sed WKY (84 ± 6%, P = 0.0067). Maximal endothelium-dependent relaxation to 10-4 M ACh was completely restored in Ex SHR (93 ± 9%) vs. Sed SHR ( P = 0.0011). Nω-nitro-l-arginine abolished endothelium-dependent relaxation in all groups ( P ≤ 0.0001) and caused equal vasocontraction to maximal ACh in Sed SHR and Ex SHR. Endothelium-independent relaxation to sodium nitroprusside was similar in all groups. Protein levels of endothelial NO synthase were higher in SHR vs. WKY ( P = 0.0157) and in Ex vs. Sed ( P = 0.0536). Protein levels of the prooxidant NAD(P)H oxidase subunit, gp91phox, were higher in SHR vs. WKY ( P < 0.0001) and were diminished in Ex vs. Sed ( P = 0.0557). Levels of the antioxidant SOD-1, -2, and catalase enzymes were lower in SHR vs. WKY (all P ≤ 0.0005) but were not altered by Ex. Thus elevated gp91phox-dependent oxidative stress and reduced antioxidant capacity likely contributed to impaired endothelium-dependent vasorelaxation in Sed SHR. Furthermore, reduced gp91phox-dependent oxidative stress and enhanced endothelial NO synthase-derived NO likely contributed to restored endothelium-dependent vasorelaxation in Ex SHR.

Antihypertensive and antioxidant effects of supplementation with red wine pomace in spontaneously hypertensive rats

2017 ◽  
Vol 8 (7) ◽  
pp. 2444-2454 ◽  
Author(s):  
Raquel Del Pino-García ◽  
María D. Rivero-Pérez ◽  
María L. González-SanJosé ◽  
Kevin D. Croft ◽  
Pilar Muñiz
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Red Wine ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
No Bioavailability ◽  
Vascular Oxidative Stress ◽  
Antioxidant Effects

4-Week supplementation with a new red wine pomace seasoning (RWPS) decreased blood pressure, ameliorated vascular oxidative stress, and improved NO bioavailability in Spontaneously Hypertensive Rats (SHR).

In Vivo Evidence for Microvascular Oxidative Stress in Spontaneously Hypertensive Rats

Hypertension ◽  
1995 ◽  
Vol 25 (5) ◽  
pp. 1083-1089 ◽  
Author(s):  
Hidekazu Suzuki ◽  
Allen Swei ◽  
Benjamin W. Zweifach ◽  
Geert W. Schmid-Schönbein
Keyword(s):  
Oxidative Stress ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

scholarly journals Immunohistochemical Analysis of 4-HNE, NGAL, and HO-1 Tissue Expression after Apocynin Treatment and HBO Preconditioning in Postischemic Acute Kidney Injury Induced in Spontaneously Hypertensive Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1163
Author(s):  
Sanjin Kovacevic ◽  
Milan Ivanov ◽  
Maja Zivotic ◽  
Predrag Brkic ◽  
Zoran Miloradovic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Spontaneously Hypertensive Rats ◽  
Kidney Injury ◽  
Immunohistochemical Analysis ◽  
Tissue Expression ◽  
Pure Oxygen ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Renal Expression

Oxidative stress has been considered as a central aggravating factor in the development of postischemic acute kidney injury (AKI). The aim of this study was to perform the immunohistochemical analysis of 4-hydroxynonenal (4-HNE), neutrophil gelatinase-associated lipocalin (NGAL), and heme oxygenase-1 (HO-1) tissue expression after apocynin (APO) treatment and hyperbaric oxygenation (HBO) preconditioning, applied as single or combined protocol, in postischemic acute kidney injury induced in spontaneously hypertensive rats (SHR). Twenty-four hours before AKI induction, HBO preconditioning was carried out by exposing to pure oxygen (2.026 bar) twice a day, for 60 min in two consecutive days. Acute kidney injury was induced by removal of the right kidney while the left renal artery was occluded for 45 min by atraumatic clamp. Apocynin was applied in a dose of 40 mg/kg body weight, intravenously, 5 min before reperfusion. We showed increased 4-HNE renal expression in postischemic AKI compared to Sham-operated (SHAM) group. Apocynin treatment, with or without HBO preconditioning, improved creatinine and phosphate clearances, in postischemic AKI. This improvement in renal function was accompanied with decreased 4-HNE, while HO-1 kidney expression restored close to the control group level. NGAL renal expression was also decreased after apocynin treatment, and HBO preconditioning, with or without APO treatment. Considering our results, we can say that 4-HNE tissue expression can be used as a marker of oxidative stress in postischemic AKI. On the other hand, apocynin treatment and HBO preconditioning reduced oxidative damage, and this protective effect might be expected even in experimental hypertensive condition.

scholarly journals Diabetes mellitus activates fetal gene program and intensifies cardiac remodeling and oxidative stress in aged spontaneously hypertensive rats

2013 ◽  
Vol 12 (1) ◽  
pp. 152 ◽  
Author(s):  
Camila Rosa ◽  
Natasha Xavier ◽  
Dijon Henrique Campos ◽  
Ana Angélica Fernandes ◽  
Marcelo Diarcadia Cezar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Cardiac Remodeling ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
And Oxidative Stress
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