scholarly journals Neonatal sympathectomy reduces NADPH oxidase activity and vascular resistance in spontaneously hypertensive rat kidneys

2006 ◽  
Vol 291 (2) ◽  
pp. R391-R399 ◽  
Author(s):  
Torsten Schlüter ◽  
Rita Grimm ◽  
Antje Steinbach ◽  
Gerd Lorenz ◽  
Rainer Rettig ◽  
...  
Keyword(s):  
Blood Flow ◽  
Arterial Pressure ◽  
Nadph Oxidase ◽  
Mrna Expression ◽  
Vascular Resistance ◽  
Oxidase Activity ◽  
Spontaneously Hypertensive ◽  
Nadph Oxidase Activity ◽  
Renal Vascular ◽  
Neonatal Sympathectomy

Neonatal sympathectomy reduces arterial pressure in spontaneously hypertensive rats (SHR). In SHR transplanted with a kidney from sympathectomized SHR, arterial pressure was lower and less Na+ sensitive than in SHR transplanted with a kidney from hydralazine-treated SHR. This study was performed to identify underlying renal mechanisms. Tests for differential renal mRNA expression of nine a priori selected genes revealed robust differences for renal medullary expression of the NADPH oxidase subunit p47phox. Therefore, we investigated the effects of neonatal sympathectomy on renal mRNA expression of NADPH oxidase subunits, NADPH oxidase activity, and renal function. In 10-wk-old sympathectomized SHR fed a 0.6% NaCl diet, medullary p47phox and gp91phox expression was 40% less than in hydralazine-treated SHR. Also, after a 1.8% NaCl diet, medullary p47phox mRNA expression was lower in sympathectomized than in hydralazine-treated SHR. We found lower cortical (−30%, P < 0.01) and medullary (−30%, P < 0.05) NADPH oxidase activities in sympathectomized than in hydralazine-treated or untreated SHR. Glomerular filtration rate, renal blood flow, medullary blood flow, and fractional Na+ excretion in kidney grafts from sympathectomized and hydralazine-treated donors ( n = 8 per group) were similar at baseline and in response to a 20-mmHg rise in renal perfusion pressure. Renal vascular resistance was lower in kidneys from sympathectomized than hydralazine-treated donors (25 ± 2 vs. 32 ± 4 mmHg·min·ml−1, P < 0.05). The results indicate that the sympathetic nervous system contributes to the level of renal NADPH oxidase activity and to perinatal programming of alterations in renal vascular function that lead to elevated renal vascular resistance in SHR.

Mechanism of action of vasoconstrictor responses to atriopeptin II in conscious SHR

1985 ◽  
Vol 249 (6) ◽  
pp. R781-R786 ◽  
Author(s):  
R. W. Lappe ◽  
J. A. Todt ◽  
R. L. Wendt
Keyword(s):  
Blood Flow ◽  
Arterial Pressure ◽  
Vascular Resistance ◽  
Regional Blood Flow ◽  
Sympathetic Nerves ◽  
Spontaneously Hypertensive ◽  
Regional Vascular Resistance ◽  
6 Hydroxydopamine ◽  
Renal Vascular ◽  
Renal Sympathetic

Previous studies have demonstrated that infusion of synthetic atriopeptin II (AP II) lowered arterial pressure, reduced regional blood flow, and increased total peripheral and regional vascular resistances in conscious spontaneously hypertensive rats (SHR). This study was designed to examine the mechanism(s) involved in regional vasoconstrictor responses to AP II. In these experiments, hemodynamic actions of AP II were examined in control, 6-hydroxydopamine-treated (chemically sympathectomized), and renal-denervated groups of instrumented conscious SHR. Infusion of AP II (1 microgram X kg-1 X min-1) caused similar reductions in mean arterial pressure in control (-22 +/- 2 mmHg), chemically sympathectomized (-23 +/- 2 mmHg), and renal-denervated (-23 +/- 3 mmHg) SHR. In control SHR, AP II infusion reduced renal (-20 +/- 3%), mesenteric (-26 +/- 2%), and hindquarters (-18 +/- 10%) blood flow and increased regional vascular resistance in all three beds. Chemical sympathectomy prevented the fall in renal blood flow (RBF) and significantly abolished the regional vasoconstrictor responses to AP II infusion. In unilateral renal-denervated groups of SHR, AP II reduced renal vascular resistance (RVR) -11 +/- 3% but failed to alter RBF (-3 +/- 1%) in denervated kidneys. In contrast, RVR increased (20 +/- 7%) and RBF was significantly reduced (-29 +/- 3%) in contralateral-innervated kidneys. This study demonstrated that chemical or surgical destruction of renal sympathetic nerves abolished AP II-induced increases in RVR. These data further indicate that in conscious SHR the regional vasoconstrictor responses to AP II infusion appear to be mediated by increases in sympathetic tone rather than through direct vascular actions of AP II.

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.

Abstract 077: Renal Denervation Attenuates Salt-Sensitive Hypertension and Oxidative Stress in Rats with Unilateral Hydronephrosis

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Maria Peleli ◽  
Ammar Al-Mashhadi ◽  
Ting Yang ◽  
Erik G Persson ◽  
Mattias Carlstrom
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Nadph Oxidase ◽  
Mrna Expression ◽  
Oxidase Activity ◽  
Renal Denervation ◽  
Urine Osmolality ◽  
Nadph Oxidase Activity ◽  
Urine Production ◽  
Salt Sensitive Hypertension

Hydronephrotic rats and mice have impaired renal function and develop salt-sensitive hypertension, which are associated with oxidative stress. Increased sympathetic nerve activity and oxidative stress in the kidney may play important roles in renovascular hypertension. This study aimed to investigate the contribution of renal sympathetic nerve activity in the development of hypertension in hydronephrosis. A partial unilateral ureteral obstruction (PUUO) was created in 3-weeks old rats to induce hydronephrosis. Surgical denervation, or sham operation, of the PUUO kidney was performed at the time of ureteral obstruction and again 4-weeks later during implantation of a telemetric blood pressure device. Hydronephrotic animals had higher blood pressure (115±3 mmHg) compared with controls (87±1 mmHg), and the blood pressure elevation to a high salt diet was more pronounced (15±2 vs 5±1 mmHg) (p<0.05). Hydronephrosis was also associated with increased urine production (40±4 μl/24h/gBW) and lower urine osmolality (1242±109 mOsm/kg H2O) compared with controls (28±3 μl/24h/gBW and 1751±83 mOsm) (p<0.05). Renal denervation in rats with PUUO attenuated hypertension (97±3 mmHg) and normalized salt-sensitivity (5±1 mmHg), urine production (32±2 μl/24h/gBW) and urine osmolality (1586±127 mOsm/kg H2O) (p<0.05). NADPH oxidase activity in renal cortex from PUUO rats was increased compared with controls (4608±396 vs 3373±217 CLU/min/mg protein) (p<0.05). This was associated with increased cortical mRNA expression of Nox2 (2.3±0.43), p22phox (2.65±0.67) and p47phox (1.39±0.23) compared with controls (p<0.05). Remarkably, denervation in PUUO rats normalized both NADPH oxidase activity (3363±258 CLU/min/mg protein) and mRNA expression of Nox2, p22phox and p47phox (p<0.05). Interestingly, also myocardial tissue from PUUO displayed increased mRNA expression of Nox2 (1.68±0.23) and p22phox (2.82±0.51) compared with control rats, and this was normalized by renal denervation (0.81±0.43) (p<0.05). In conclusion, renal denervation of the hydronephrotic kidney attenuates hypertension and salt-sensitivity, and restores renal excretion pattern. Mechanistically, this is associated with reduced renal NADPH oxidase activity and expression.

scholarly journals Losartan does not decrease renal oxygenation and norepinephrine effects in rats after resuscitated hemorrhage

2018 ◽  
Vol 315 (2) ◽  
pp. F241-F246
Author(s):  
Sofia Jönsson ◽  
Jacqueline M. Melville ◽  
Mediha Becirovic-Agic ◽  
Michael Hultström
Keyword(s):  
Blood Flow ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Renal Blood Flow ◽  
Oxygen Tension ◽  
Vascular Resistance ◽  
Renal Vascular Resistance ◽  
Renal Oxygen Consumption ◽  
Significant Difference ◽  
Renal Vascular

Renin-angiotensin-system blockers are thought to increase the risk of acute kidney injury after surgery and hemorrhage. We found that losartan does not cause renal cortical hypoxia after hemorrhage in rats because of decreased renal vascular resistance, but we did not evaluate resuscitation. We aimed to study losartan’s effect on renal cortical and medullary oxygenation, as well as norepinephrine’s vasopressor effect in a model of resuscitated hemorrhage. After 7 days of losartan (60 mg·kg−1·day−1) or control treatment, male Wistar rats were hemorrhaged 20% of their blood volume and resuscitated with Ringerʼs acetate. Mean arterial pressure, renal blood flow, and kidney tissue oxygenation were measured at baseline and after resuscitation. Finally, the effect of norepinephrine on mean arterial pressure and renal blood flow was investigated. As expected, losartan lowered mean arterial pressure but not renal blood flow. Losartan did not affect renal oxygen consumption and oxygen tension. Mean arterial pressure and renal blood flow were lower after resuscitated hemorrhage. A smaller increase of renal vascular resistance in the losartan group translated to a smaller decrease in cortical oxygen tension, but no significant difference was seen in medullary oxygen tension, either between groups or after hemorrhage. The effect of norepinephrine on mean arterial pressure and renal blood flow was similar in control- and losartan-treated rats. Losartan does not decrease renal oxygenation after resuscitated hemorrhage because of a smaller increase in renal vascular resistance. Further, losartan does not decrease the efficiency of norepinephrine as a vasopressor, indicating that blood pressure may be managed effectively during losartan treatment.

Sympathetic-renal interaction in chronic arterial pressure control

2002 ◽  
Vol 283 (2) ◽  
pp. R441-R450 ◽  
Author(s):  
Olaf Grisk ◽  
Hans-Joachim Rose ◽  
Gerd Lorenz ◽  
Rainer Rettig
Keyword(s):  
Arterial Pressure ◽  
Pressure Rise ◽  
Pressure Control ◽  
Sympathetic Tone ◽  
F1 Hybrids ◽  
Kidney Graft ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Renal Vascular ◽  
Neonatal Sympathectomy

The effects of neonatal sympathectomy of donors or recipients on posttransplantation arterial pressure were investigated in spontaneously hypertensive rats (SHR) by renal transplantation experiments. Conscious mean arterial pressure (MAP) and renal vascular resistance were 136 ± 1 mmHg and 15.5 ± 1.2 mmHg · ml−1 · min · g in sympathectomized SHR ( n = 8) vs. 158 ± 4 mmHg ( P < 0.001) and 20.8 ± 1.1 mmHg · ml−1 · min · g ( P < 0.05) in controls ( n = 10). Seven weeks after transplantation of a kidney from neonatally sympathectomized SHR donors, MAP in SHR recipients ( n = 10) was 20 mmHg lower than in controls transplanted with a kidney from hydralazine-treated SHR ( n = 10) ( P < 0.05) associated with reduced sodium sensitivity of MAP. Neonatal sympathectomy also lowered MAP in F1-hybrids (F1H; SHR × Wistar-Kyoto rats). Within 6 wk after transplantation, renal grafts from untreated SHR increased MAP by 20 mmHg in sympathectomized F1H ( n = 10) and by 35 mmHg in sham-treated F1H ( n = 8) ( P < 0.05). Neonatal sympathectomy induces chronic changes in SHR kidney function leading to a MAP reduction even when extrarenal sympathetic tone is restored. Generalized reduction in sympathetic tone resets the kidney-fluid system to reduced MAP and blunts the extent of arterial pressure rise induced by an SHR kidney graft.

scholarly journals Blockade of TGF-β1 Signalling Inhibits Cardiac NADPH Oxidase Overactivity in Hypertensive Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
José Luis Miguel-Carrasco ◽  
Ana Baltanás ◽  
Carolina Cebrián ◽  
María U. Moreno ◽  
Begoña López ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Chronic Administration ◽  
Collagen Type I ◽  
Type I ◽  
Hypertensive Rats ◽  
Nadph Oxidases ◽  
Spontaneously Hypertensive ◽  
Nadph Oxidase Activity ◽  
Wistar Kyoto

NADPH oxidases constitute a major source of superoxide anion (⋅O2 -) in hypertension. Several studies suggest an important role of NADPH oxidases in different effects mediated by TGF-β 1. In this study we show that chronic administration of P144, a peptide synthesized from type III TGF-β 1 receptor, significantly reduced the cardiac NADPH oxidase expression and activity as well as in the nitrotyrosine levels observed in control spontaneously hypertensive rats (V-SHR) to levels similar to control normotensive Wistar Kyoto rats. In addition, P144 was also able to reduce the significant increases in the expression of collagen type I protein and mRNA observed in hearts from V-SHR. In addition, positive correlations between collagen expression, NADPH oxidase activity, and nitrotyrosine levels were found in all animals. Finally, TGF-β 1-stimulated Rat-2 exhibited significant increases in NADPH oxidase activity that was inhibited in the presence of P144. It could be concluded that the blockade of TGF-β 1 with P144 inhibited cardiac NADPH oxidase in SHR, thus adding new data to elucidate the involvement of this enzyme in the profibrotic actions of TGF-β 1.

Abstract P063: Pitavastatin Has Antihypertensive and Renoprotective Effects With Upregulation of No System and Down-regulation of Oxidative Stress in the Kidney of Spontaneously Hypertensive Rats

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Gaizun Hu ◽  
Osamu Ito ◽  
Rong Rong ◽  
Bin Xu ◽  
Akihiro Sakuyama ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Active Form ◽  
Thiobarbituric Acid ◽  
Down Regulation ◽  
Spontaneously Hypertensive ◽  
Nadph Oxidase Activity ◽  
Enos Phosphorylation

Clinical trials have demonstrated renoprotective effects of atorvastatin (ATV) and pitavastatin (PTV), which belong to the strong statins, are more potent than other statins. We reported previously that ATV attenuated the development of hypertension in SHR with increasing the endothelial and neuronal NO synthases (eNOS, nNOS) expressions in the kidney, whereas ATV inhibited the eNOS phosphorylation at serin1177 (J Hypertes 28: 2278-2288, 2010). To clarify the mechanisms of renoprotective effects of PTV, the present study examined the effects of PTV on blood pressure, renal functions, NOS and oxidative stress in the kidney of SHR. Five-week-old, male SHR were given orally PTV (2mg/kg/day) or vehicle for 8 weeks. The systolic blood pressure (SBP) was measured. The NOS expression and eNOS phosphorylation were analyzed by Western blot. The NADPH oxidase activity was measured by the lucigenin-enhanced chemiluminescence method. PTV attenuated the progression of hypertension (220 ± 8 vs. 177± 4 mmHg, P<0.01) and albuminuria (684 ± 66 vs. 398 ± 42 mg/day, P<0.01) without changing plasma total cholesterol or creatinine. PTV increased the eNOS and nNOS expressions in the outer and inner medulla of the kidney (eNOS; by 182% and 186%, nNOS; by 315% and 194%, P<0.01). PTV significantly stimulated the eNOS phosphorylation at serin1177 in the inner medulla and inhibited the eNOS phosphorylation at threonine495 in the outer and inner medulla. PTV decreased hydrogen peroxide (13.4 ± 2.1 vs. 6.1 ± 1.2 nmol/day, P<0.05) and thiobarbituric acid reactive substances (TBARS) (236.6 ± 12.4 vs. 198.3 ± 10.6 nmol/day, P<0.05) in the urine and the NADPH oxidase activity (42681± 2515 vs. 32381 ± 1995 c.p.m/mg protein, P<0.01) in the renal cortex. These results indicate that PTV attenuates the development of hypertension and albuminuria in SHR with increasing the eNOS and nNOS expressions, changing the eNOS phosphorylation to an active form and mitigating oxidative stress in the kidney. The antihypertensive and renoprotective effects of PTV may be mediated in part by an upregulation of NO system and down-regulation of oxidative stress in the kidney.

scholarly journals Endothelial actin depolymerization mediates NADPH oxidase-superoxide production during flow reversal

2014 ◽  
Vol 306 (1) ◽  
pp. H69-H77 ◽  
Author(s):  
Jenny S. Choy ◽  
Xiao Lu ◽  
Junrong Yang ◽  
Zhen-Du Zhang ◽  
Ghassan S. Kassab
Keyword(s):  
Blood Flow ◽  
Shear Stress ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Fold Increase ◽  
Flow Reversal ◽  
Ros Production ◽  
Reversed Flow ◽  
Nadph Oxidase Activity ◽  
Actin Depolymerization

Slow moving blood flow and changes in flow direction, e.g., negative wall shear stress, can cause increased superoxide (O2·−) production in vascular endothelial cells. The mechanism by which shear stress increases O2·− production, however, is not well established. We tested the hypothesis that actin depolymerization, which occurs during flow reversal, mediates O2·− production in vascular endothelial cells via NADPH oxidase, and more specifically, the subunit p47phox. Using a swine model, we created complete blood flow reversal in one carotid artery, while the contralateral vessel maintained forward blood flow as control. We measured actin depolymerization, NADPH oxidase activity, and reactive oxygen species (ROS) production in the presence of various inhibitors. Flow reversal was found to induce actin depolymerization and a 3.9 ± 1.0-fold increase in ROS production as compared with forward flow. NADPH oxidase activity was 1.4 ± 0.2 times higher in vessel segments subjected to reversed blood flow when measured by a direct enzyme assay. The NADPH oxidase subunits gp91phox (Nox2) and p47phox content in the vessels remained unchanged after 4 h of flow reversal. In contrast, p47phox phosphorylation was increased in vessels with reversed flow. The response caused by reversed flow was reduced by in vivo treatment with jasplakinolide, an actin stabilizer (only a 1.7 ± 0.3-fold increase). Apocynin (an antioxidant) prevented reversed flow-induced ROS production when the animals were treated in vivo. Cytochalasin D mimicked actin depolymerization in vitro and caused a 5.2 ± 3.0-fold increase in ROS production. These findings suggest that actin filaments play an important role in negative shear stress-induced ROS production by potentiating NADPH oxidase activity, and more specifically, the p47phox subunit in vascular endothelium.

Role of 12/15-lipoxygenase in the expression of MCP-1 in mouse macrophages

2008 ◽  
Vol 294 (4) ◽  
pp. H1933-H1938 ◽  
Author(s):  
Yeshao Wen ◽  
Jiali Gu ◽  
George E. Vandenhoff ◽  
Xiaoping Liu ◽  
Jerry L. Nadler
Keyword(s):  
Protein Kinase ◽  
Nadph Oxidase ◽  
Mrna Expression ◽  
Cell Line ◽  
Oxidase Activity ◽  
Mitogen Activated Protein Kinase ◽  
Macrophage Cell Line ◽  
Macrophage Cell ◽  
Nadph Oxidase Activity

Monocyte chemoattractant protein (MCP)-1 plays a key role in atherosclerosis and inflammation associated with visceral adiposity by inducing mononuclear cell migration. Evidence shows that mouse peritoneal macrophages (MPM) express a 12-lipoxygenase (12/15-LO) that has been clearly linked to accelerated atherosclerosis in mouse models and increased monocyte endothelial interactions in both rodent and human cells. However, the role of 12/15-LO products in regulating MCP-1 expression in macrophages has not been clarified. In this study, we tested the role of 12/15-LO products using MPM and the mouse macrophage cell line, J774A.1 cells. We found that 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] increased MCP-1 mRNA and protein expression in J774A.1 cells and MPM. In contrast, 12(R)-HETE, a lipid not derived from 12/15-LO, did not affect MCP-1 expression. 15(S)-HETE also increased MCP-1 mRNA expression, but the effect was less compared with 12(S)-HETE. MCP-1 mRNA expression was upregulated in a macrophage cell line stably overexpressing 12/15-LO (Plox-86 cells) and in MPM isolated from a 12/15-LO transgenic mouse. In addition, the expression of MCP-1 was downregulated in MPM isolated from 12/15-LO knockout mice. 12(S)-HETE-induced MCP-1 mRNA expression was attenuated by specific inhibitors of protein kinase C (PKC) and p38 mitogen-activated protein kinase (p38). 12(S)-HETE also directly activated NADPH oxidase activity. Two NADPH oxidase inhibitors, apocynin and diphenyleneiodonium chloride, blocked 12(S)-HETE-induced MCP-1 mRNA. Apocynin attenuated 12(S)-HETE-induced MCP-1 protein secretion. These data show that 12(S)-HETE increases MCP-1 expression by inducing PKC, p38, and NADPH oxidase activity. These results suggest a potentially important mechanism linking 12/15-LO activation to MCP-1 expression that induces inflammatory cell infiltration.

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