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.

scholarly journals Combination of Exercise Training and SOD Mimetic Tempol Enhances Upregulation of Nitric Oxide Synthase in the Kidney of Spontaneously Hypertensive Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Pengyu Cao ◽  
Osamu Ito ◽  
Daisuke Ito ◽  
Rong Rong ◽  
Yang Zheng ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Exercise Training ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Sod Activity ◽  
Spontaneously Hypertensive ◽  
Nadph Oxidase Activity ◽  
Expression Levels

Both exercise training (Ex) and superoxide dismutase (SOD) mimetic tempol have antihypertensive and renal protective effects in rodent models of several hypertensions. We recently reported that Ex increases nitric oxide (NO) production and the expression levels of endothelial and neuronal NO synthase (eNOS and nNOS) in the kidney and aorta of the spontaneously hypertensive rats (SHR) and normotensive Wistar–Kyoto rats (WKY). We also found that endogenous hydrogen peroxide (H2O2) upregulates the expression levels of eNOS and nNOS in SHR. To elucidate the mechanism of the Ex-upregulated NO system in the kidney, we examined the additive effect of Ex and tempol on the renal NO system in SHR and WKY. Our data showed that, in SHR, both Ex and tempol increase the levels of H2O2 and nitrate/nitrite (NOx) in plasma and urine. We also observed an increased renal NOS activity and upregulated expression levels of eNOS and nNOS with decreased NADPH oxidase activity. The effects of the combination of Ex and tempol on these variables were cumulate in SHR. On the other hand, we found that Ex increases these variables with increased renal NADPH oxidase activity, but tempol did not change these variables or affect the Ex-induced upregulation in the activity and expression of NOS in WKY. The SOD activity in the kidney and aorta was activated by tempol only in SHR, but not in WKY; whereas Ex increased SOD activity only in the aorta in both SHR and WKY. These results indicate that Ex-induced endogenous H2O2 produced in the blood vessel and other organs outside of the kidney may be carried to the kidney by blood flow and stimulates the NO system in the kidney.

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.

Aerobic exercise training improves oxidative stress and ubiquitin proteasome system activity in heart of spontaneously hypertensive rats

2015 ◽  
Vol 402 (1-2) ◽  
pp. 193-202 ◽  
Author(s):  
Luiz Henrique Soares de Andrade ◽  
Wilson Max Almeida Monteiro de Moraes ◽  
Eduardo Hiroshi Matsuo Junior ◽  
Elizabeth de Orleans Carvalho de Moura ◽  
Hanna Karen Moreira Antunes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Exercise Training ◽  
Aerobic Exercise ◽  
Spontaneously Hypertensive Rats ◽  
Ubiquitin Proteasome System ◽  
Aerobic Exercise Training ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
System Activity ◽  
Ubiquitin Proteasome

scholarly journals Increased Blood Pressure Causes Lymphatic Endothelial Dysfunction via Oxidative Stress in Spontaneously Hypertensive Rats

Hypertension ◽  
2020 ◽  
Vol 76 (2) ◽  
pp. 598-606
Author(s):  
Masashi Mukohda ◽  
Risuke Mizuno ◽  
Hiroshi Ozaki
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Nadph Oxidase ◽  
Sodium Nitroprusside ◽  
P38 Mapk ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

The lymphatic system is involved in the pathogenesis of edema, inflammation, and cancer metastasis. Because lymph vessels control fluid electrolytes and volume balance, changes in lymphatic activity can be expected to alter systemic blood pressure. This study examined possible changes in lymphatic contractile properties in spontaneously hypertensive rats (SHR). Thoracic ducts isolated from 10- to 12-week-old SHR exhibited either decreased acetylcholine-induced endothelium-dependent relaxation or sodium nitroprusside-induced endothelium-independent relaxation compared with age-matched Wister-Kyoto rats. The impairment in acetylcholine responsiveness was more pronounced than sodium nitroprusside responsiveness. N-Nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor blunted acetylcholine-induced relaxation in Wister-Kyoto rats, indicating an involvement of endothelial nitric oxide production. Endothelial dysfunction in lymph vessels of SHR was attenuated by tempol (a superoxide dismutase mimetic), apocynin, or VAS-2870 (NADPH oxidase inhibitors). Consistent with these observations, nitrotyrosine levels were significantly elevated in SHR, indicative of increased oxidative stress. In addition, protein expression of NADPH oxidase 2 and phosphorylation of p47 phox (Ser345) were significantly increased in SHR. Further, SB203580 (a p38 MAPK inhibitor) restored the acetylcholine-induced relaxation in SHR. It is notable that 4-week-old SHR, which exhibited normal blood pressure, did not show any decreased activity of acetylcholine- or sodium nitroprusside-induced relaxation. Additionally, antihypertensive treatment of 4-week-old SHR with hydrochlorothiazide and reserpine or hydrochlorothiazide and hydralazine for 6 weeks completely restored lymphatic endothelial dysfunction. We conclude that contractile activity of lymphatic vessels is functionally impaired with the development of increasing blood pressure, which is mediated through increased oxidative stress via the p38 MAPK/NADPH oxidase 2 pathway.

Does a general alteration in nitric oxide synthesis system occur in spontaneously hypertensive rats?

1994 ◽  
Vol 266 (1) ◽  
pp. H272-H278 ◽  
Author(s):  
J. Xiao ◽  
P. K. Pang
Keyword(s):  
Nitric Oxide ◽  
Spontaneously Hypertensive Rats ◽  
No Synthase ◽  
Hypertensive Rats ◽  
Synthesis System ◽  
Spontaneously Hypertensive ◽  
Proliferation Of Lymphocytes ◽  
General Activation ◽  
Wistar Kyoto ◽  
Synthase Inhibitor

Immune dysfunction has been reported in spontaneously hypertensive rats (SHR). The current study investigated interactions between macrophages or vascular smooth muscle cells (VSMC) and lymphocytes in SHR and examined the role of nitric oxide (NO) in this interaction. SHR macrophages significantly inhibited the proliferation of lymphocytes from SHR and the genetic control, Wistar-Kyoto rats (WKY). This inhibition was reversed by a NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA). SHR VSMC also significantly inhibited the proliferation responses of lymphocytes from SHR and WKY. The inhibition was cell density dependent. In addition, L-NMMA fully reversed the inhibition by SHR VSMC. Upon stimulation, the macrophages and VSMC from SHR produced a significantly higher amount of NO compared with those from WKY. These results suggest that the overproduction of NO was involved in the interaction between macrophages or VSMC and lymphocytes in SHR. Increased NO synthase activity in macrophages and VSMC may indicate a general activation of the NO synthesis system in SHR. The alteration of the NO synthesis system may be an important factor contributing to the lymphocyte depression in hypertension.

scholarly journals Exercise training improves functional sympatholysis in spontaneously hypertensive rats through a nitric oxide-dependent mechanism

2014 ◽  
Vol 307 (2) ◽  
pp. H242-H251 ◽  
Author(s):  
Masaki Mizuno ◽  
Gary A. Iwamoto ◽  
Wanpen Vongpatanasin ◽  
Jere H. Mitchell ◽  
Scott A. Smith
Keyword(s):  
Nitric Oxide ◽  
Exercise Training ◽  
Muscle Contraction ◽  
Spontaneously Hypertensive Rats ◽  
Wheel Running ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Functional Sympatholysis ◽  
Dependent Mechanism ◽  
Voluntary Wheel

Functional sympatholysis is impaired in hypertensive animals and patients. Exercise training (ET) improves functional sympatholysis through a nitric oxide (NO)-dependent mechanism in normotensive rats. However, whether ET has similar physiological benefits in hypertension remains to be elucidated. Thus we tested the hypothesis that the impairment in functional sympatholysis in hypertension is reversed by ET through a NO-dependent mechanism. In untrained normotensive Wistar-Kyoto rats (WKYUT; n = 13), untrained spontaneously hypertensive rats (SHRUT; n = 13), and exercise-trained SHR (SHRET; n = 6), changes in femoral vascular conductance (FVC) were examined during lumbar sympathetic nerve stimulation (1, 2.5, and 5 Hz) at rest and during muscle contraction. The magnitude of functional sympatholysis (Δ%FVC = Δ%FVC muscle contraction − Δ%FVC rest) in SHRUT was significantly lower than WKYUT (1 Hz: −2 ± 4 vs. 13 ± 3%; 2.5 Hz: 9 ± 3 vs. 21 ± 3%; and 5 Hz: 12 ± 3 vs. 26 ± 3%, respectively; P < 0.05). Three months of voluntary wheel running significantly increased maximal oxygen uptake in SHRET compared with nontrained SHRUT (78 ± 6 vs. 62 ± 4 ml·kg−1·min−1, respectively; P < 0.05) and restored the magnitude of functional sympatholysis in SHRET (1 Hz: 9 ± 2%; 2.5 Hz: 20 ± 4%; and 5 Hz: 34 ± 5%). Blockade of NO synthase (NOS) by NG-nitro-l-arginine methyl ester attenuated functional sympatholysis in WKYUT but not SHRUT. Furthermore, NOS inhibition significantly diminished the improvements in functional sympatholysis in SHRET. These data demonstrate that impairments in functional sympatholysis are normalized via a NO mechanism by voluntary wheel running in hypertensive rats.

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