Effect of p22phox depletion on sympathetic regulation of blood pressure in SHRSP: evaluation in a new congenic strain

Zahid, Hasan M.; Ferdaus, Mohammed Z.; Ohara, Hirotaka; Isomura, Minoru; Nabika, Toru

doi:10.1038/srep36739

Cited by 4 publications

(3 citation statements)

References 28 publications

(46 reference statements)

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“…The RVLM was chemically identified by a pressor response (>20 mmHg) to L-glutamate (1 nmol) microinjection. The changes in BP, HR, and renal sympathetic nerve activity (RSNA) were recorded 10 min after injection of Tempol (5 nmol), which was based on the previous study (Wang et al, 2016 ; Zahid et al, 2016 ). At the end of each experiment, 100 nl of 2% pontamine sky blue solution was injected into the RVLM to mark the site.…”

Section: Methodsmentioning

confidence: 99%

Oxidative Stress in the Rostral Ventrolateral Medulla Contributes To Cardiovascular Regulation in Preeclampsia

et al. 2017

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Background: It has been demonstrated that preeclampsia, a pregnancy-specific hypertension disorder, is characterized by high blood pressure (BP) and sympathetic overactivity. Increased reactive oxygen species (ROS) in the rostral ventrolateral medulla (RVLM), a key region for controlling sympathetic tone, has been reported to contribute to high level of BP and sympathetic outflow. The aim of the present study was to determine the role of the RVLM ROS in mediating the preeclampsia-associated cardiovascular dysfunction.Methods: The animal model of preeclampsia was produced by administration of desoxycorticosterone acetate (DOCA) to pregnant rats.Results: Compared with normal pregnant rats without DOCA treatment (NP), the protein concentration and norepinephrine excretion in 24-h urine, as well as BP in pregnant rats with DOCA treatment (PDS) were significantly increased. The levels of superoxide anion and the protein expression of NADPH oxidase subtype (NOX4) in the RVLM were significantly increased in PDS than in NP groups. Furthermore, microinjection of the superoxide dismutase (SOD) mimic Tempol (5 nmol) into the RVLM significantly decreased BP, heart rate, and renal sympathetic never activity in PDS but not in NP group.Conclusion: The present data suggest that high BP and sympathetic overactivity in preeclampsia rats is associated with increased oxidative stress in the RVLM via upregulation of NOX4 expression.

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Section: Methodsmentioning

confidence: 99%

Oxidative Stress in the Rostral Ventrolateral Medulla Contributes To Cardiovascular Regulation in Preeclampsia

et al. 2017

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“…Urinary 15-isoprostane-F2t (IsoP) excretion level was measured to estimate oxidative stress [13] using an ELISA kit (JaICA, Nikken SEIL Co., Ltd.). Urinary protein level was determined in 24h urine samples as well with the protein assay BCA kit (Wako Pure Chemical Industries Ltd., Japan) [14]. The measurements were performed according to the manufacturer's protocol.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of Pathological Association between Stroke-Related QTL and Salt-Induced Renal Injury in Stroke-Prone Spontaneously Hypertensive Rat

Reza

Ngarashi

Koike

et al. 2019

BioMed Research International

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The stroke-prone spontaneously hypertensive rat (SHRSP) suffers from severe hypertension and hypertensive organ damage such as cerebral stroke and kidney injury under salt-loading. By a quantitative trait locus (QTL) analysis between SHRSP and SHR (the stroke-resistant parental strain of SHRSP), two major QTLs for stroke susceptibility were identified on chromosomes 1 and 18 of SHRSP, which were confirmed in congenic strains constructed between SHRSP and SHR. As the progression of renal dysfunction was suggested to be one of the key factors inducing stroke in SHRSP, we examined effects of the stroke-related QTLs on kidney injury using two congenic strains harboring either of SHRSP-derived fragments of chromosomes 1 and 18 in the SHR genome. The congenic strains were challenged with 1% NaCl solution for 4 weeks; measurement of systolic blood pressure and urinary isoprostane level (a marker for oxidative stress) and evaluation of renal injury by quantification of genetic marker expression and histological examination were performed. We found that the congenic rats with SHRSP-derived fragment of chromosome 18 showed more severe renal damage with higher expression of Col1α-1 (a genetic marker for renal fibrosis) and higher urinary isoprostane level. In contrast, the fragment of chromosome 1 from SHRSP did not give such effects on SHR. Blood pressure was not greater in either of the congenic strains when compared with SHR. We concluded that the QTL region on chromosome 18 might deteriorate salt-induced renal injury in SHR through a blood pressure-independent mechanism.

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“…These results highlight the complexities regarding the interactions between Nox activity and blood pressure regulation. Furthermore, one of the authors’ group reported that blood pressure response to glutamate microinjection into the rostral ventrolateral medulla was significantly greater in SHRSP than in SP.MES, SHR and WKY, suggesting that higher oxidative stress or Nox activity in the regulatory center of the sympathetic nerve activity in SHRSP [ 87 ].…”

Section: Experimental Models Of Strokementioning

confidence: 99%

NADPH Oxidase-Related Pathophysiology in Experimental Models of Stroke

Yao

Ago

Kitazono

et al. 2017

IJMS

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Several experimental studies have indicated that nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) exert detrimental effects on ischemic brain tissue; Nox-knockout mice generally exhibit resistance to damage due to experimental stroke following middle cerebral artery occlusion (MCAO). Furthermore, our previous MCAO study indicated that infarct size and blood-brain barrier breakdown are enhanced in mice with pericyte-specific overexpression of Nox4, relative to levels observed in controls. However, it remains unclear whether Nox affects the stroke outcome directly by increasing oxidative stress at the site of ischemia, or indirectly by modifying physiological variables such as blood pressure or cerebral blood flow (CBF). Because of technical problems in the measurement of physiological variables and CBF, it is often difficult to address this issue in mouse models due to their small body size; in our previous study, we examined the effects of Nox activity on focal ischemic injury in a novel congenic rat strain: stroke-prone spontaneously hypertensive rats with loss-of-function in Nox. In this review, we summarize the current literature regarding the role of Nox in focal ischemic injury and discuss critical issues that should be considered when investigating Nox-related pathophysiology in animal models of stroke.

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Effect of p22phox depletion on sympathetic regulation of blood pressure in SHRSP: evaluation in a new congenic strain

Cited by 4 publications

References 28 publications

Oxidative Stress in the Rostral Ventrolateral Medulla Contributes To Cardiovascular Regulation in Preeclampsia

Oxidative Stress in the Rostral Ventrolateral Medulla Contributes To Cardiovascular Regulation in Preeclampsia

Evaluation of Pathological Association between Stroke-Related QTL and Salt-Induced Renal Injury in Stroke-Prone Spontaneously Hypertensive Rat

NADPH Oxidase-Related Pathophysiology in Experimental Models of Stroke

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