Relationship between sodium balance and renal innervation during hypertension development in the spontaneously hypertensive rat

Essential hypertension is the leading cause of premature death worldwide. However, hypertension’s cause remains uncertain. endoplasmic reticulum (ER) stress has recently been associated with hypertension, but it is unclear whether ER stress causes hypertension. To clarify this question, we examined if ER stress occurs in blood vessels before the development of hypertension and if ER stress inhibition would prevent hypertension development. We used the spontaneously hypertensive rat (SHR) as a model of human essential hypertension and the Wistar-Kyoto (WKY) rat as its normotensive control. Resistance arteries collected from young rats determined that ER stress was present in SHR vessels before the onset of hypertension. To assess the effect of ER stress inhibition on hypertension development, another subset of rats were treated with 4-phenylbutyric acid (4-PBA; 1 g·kg−1·day−1) for 8 wk from 5 wk of age. Blood pressure was measured via radiotelemetry and compared with untreated SHR and WKY rats. Mesenteric resistance arteries were collected and assessed for structural and functional changes associated with hypertension. Systolic and diastolic blood pressures were significantly lower in the 4-PBA-treated SHR groups than in untreated SHRs. Additionally, 4-PBA significantly decreased the media-to-lumen ratio and ER stress marker expression, improved vasodilatory response, and reduced contractile responses in resistance arteries from SHRs. Overall, ER stress inhibition blunted the development of hypertension in the SHR. These data add evidence to the hypothesis that a component of hypertension in the SHR is caused by ER stress. NEW & NOTEWORTHY In this study, 4-phenylbutyric acid’s (4-PBA’s) molecular chaperone capability was used to inhibit endoplasmic reticulum (ER) stress in the small arteries of young spontaneously hypertensive rats (SHRs) and reduce their hypertension. These effects are likely mediated through 4-PBA's effects to reduce resistant artery contractility and increase nitric oxide-mediated endothelial vasodilation through a process preventing endothelial dysfunction. Overall, ER stress inhibition blunted the development of hypertension in this young SHR model. This suggests that a component of the increase in blood pressure found in SHRs is due to ER stress. However, it is important to note that inhibition of ER stress was not able to fully restore the blood pressure to normal, suggesting that a component of hypertension may not be due to ER stress. This study points to the inhibition of ER stress as an important new physiological pathway to lower blood pressure, where other known approaches may not achieve blood pressure-lowering targets.

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EFFECT OF CROSS-FOSTERING ON NEONATAL SODIUM BALANCE AND ADULT BLOOD PRESSURE IN THE SPONTANEOUSLY HYPERTENSIVE RAT

Clinical and Experimental Pharmacology and Physiology ◽

10.1111/j.1440-1681.1998.tb02178.x ◽

1998 ◽

Vol 25 (12) ◽

pp. 1024-1031 ◽

Cited By ~ 14

Author(s):

Ingrid Gouldsborough ◽

Nick Ashton

Keyword(s):

Blood Pressure ◽

Spontaneously Hypertensive Rat ◽

Sodium Balance ◽

Spontaneously Hypertensive ◽

Hypertensive Rat ◽

Cross Fostering

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Sodium balance during development of hypertension in the spontaneously hypertensive rat (SHR)

Acta Physiologica Scandinavica ◽

10.1111/j.1748-1716.1982.tb07084.x ◽

1982 ◽

Vol 115 (3) ◽

pp. 317-323 ◽

Cited By ~ 17

Author(s):

STEFAN LUNDIN ◽

HANS HERLITZ ◽

MARGARETA HALLBÄCK-NORDLANDER ◽

SVEN-ERIK RICKSTEN ◽

GUNNAR GÖTHBERG ◽

...

Keyword(s):

Spontaneously Hypertensive Rat ◽

Sodium Balance ◽

Spontaneously Hypertensive ◽

Hypertensive Rat

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Epitranscriptomic mechanisms of N6-methyladenosine methylation regulating mammalian hypertension development by determined spontaneously hypertensive rats pericytes

Epigenomics ◽

10.2217/epi-2019-0148 ◽

2019 ◽

Vol 11 (12) ◽

pp. 1359-1370 ◽

Cited By ~ 5

Author(s):

Qingbin Wu ◽

Xiaochen Yuan ◽

Ruiqin Han ◽

Honggang Zhang ◽

Ruijuan Xiu

Keyword(s):

High Throughput Sequencing ◽

Spontaneously Hypertensive Rat ◽

Biological Processes ◽

Spontaneously Hypertensive ◽

Hypertensive Rat ◽

Sequence Region ◽

Wistar Kyoto Rat ◽

Wistar Kyoto ◽

Hypertension Development

Aim: Pericytes maintain homeostatic functions in the blood–brain barrier. N6-methyladenosine (m6A) is critical for various biological processes, but the role of mRNA m6A methylation in hypertension has not been fully elucidated. Methods: The m6A methylation levels of Wistar Kyoto rat pericytes and spontaneously hypertensive rat pericytes were detected via m6A high-throughput sequencing. Results: The m6A methylations were more enriched in the coding sequence region, 3′UTR and 5′UTR of mRNAs, with the m6A motifs being relatively conserved across the different conditions investigated. The average m6A abundance of spontaneously hypertensive rat pericytes exhibited global reductions in the pericytes. Conclusion: This study revealed the m6A landscapes and identified an epitranscriptomic mechanism during the development of mammalian hypertension.

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Treating the Network: Application of a Combination of Two microRNA Inhibitors to the Brainstem Prevents Hypertension Development in the Spontaneously Hypertensive Rat

The FASEB Journal ◽

10.1096/fasebj.2018.32.1_supplement.847.9 ◽

2018 ◽

Vol 32 (S1) ◽

Author(s):

Jon Gorky ◽

Danielle DeCicco ◽

Sirisha Achanta ◽

James Schwaber ◽

Rajanikanth Vadigepalli

Keyword(s):

Spontaneously Hypertensive Rat ◽

Spontaneously Hypertensive ◽

Hypertensive Rat ◽

Network Application ◽

Hypertension Development

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Water deprivation-induced sodium appetite and differential expression of encephalic c-Fos immunoreactivity in the spontaneously hypertensive rat

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00359.2009 ◽

2010 ◽

Vol 298 (5) ◽

pp. R1298-R1309 ◽

Cited By ~ 13

Author(s):

Daniela T. B. Pereira-Derderian ◽

Regina C. Vendramini ◽

José V. Menani ◽

Laurival A. De Luca

Keyword(s):

Water Intake ◽

Water Deprivation ◽

Spontaneously Hypertensive Rat ◽

Area Postrema ◽

Cell Activity ◽

Sodium Balance ◽

Lamina Terminalis ◽

Spontaneously Hypertensive ◽

Sodium Appetite ◽

Hypertensive Rat

The spontaneously hypertensive rat (SHR) has an intense consumption of NaCl solution. Water deprivation (WD) followed by water intake to satiety induces partial rehydration (PR)—the WD-PR protocol—and sodium appetite. In the present work, WD produced similar water intake and no alterations in arterial pressure among spontaneously hypertensive rat (SHR), Wistar-Kyoto, and Holtzman strains. It also increased the number of cells with positive c-Fos immunoreactivity (Fos-IR) in the lamina terminalis and in the hypothalamic supraoptic (SON) and paraventricular (parvocellular, PVNp) nucleus in these strains. The WD and WD-PR produced similar alterations in all strains in serum osmolality and protein, plasma renin activity, and sodium balance. The SHR ingested about 10 times more 0.3 M NaCl than normotensives strains in the sodium appetite test that follows WD-PR. After WD-PR, the Fos-IR persisted, elevated in the lamina terminalis of all strains but notably in the subfornical organ of the SHR. The WD-PR reversed Fos-IR in the SON of all strains and in the PVNp of SHR. It induced Fos-IR in the area postrema and in the nucleus of the solitary tract (NTS), dorsal raphe, parabrachial (PBN), pre-locus coeruleus (pre-LC), suprachiasmatic, and central amygdalar nucleus of all strains. This effect was bigger in the caudal-NTS, pre-LC, and medial-PBN of SHRs. The results indicate that WD-PR increases cell activity in the forebrain and hindbrain areas that control sodium appetite in the rat. They also suggest that increased cell activity in facilitatory brain areas precedes the intense 0.3 M NaCl intake of the SHR in the sodium appetite test.

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