scholarly journals Water deprivation-partial rehydration induces sensitization of sodium appetite and alteration of hypothalamic transcripts

2016 ◽  
Vol 310 (1) ◽  
pp. R15-R23 ◽  
Author(s):  
Daniela T. B. Pereira-Derderian ◽  
Regina C. Vendramini ◽  
José V. Menani ◽  
Silvana Chiavegatto ◽  
Laurival A. De Luca
Keyword(s):  
Water Deprivation ◽  
Behavioral Plasticity ◽  
Spontaneously Hypertensive Rat ◽  
Sodium Intake ◽  
Renin Angiotensin System ◽  
Male Adult ◽  
Spontaneously Hypertensive ◽  
Sodium Appetite ◽  
Wistar Kyoto ◽  
The Brain

iSodium intake occurs either as a spontaneous or induced behavior, which is enhanced, i.e., sensitized, by repeated episodes of water deprivation followed by subsequent partial rehydration (WD-PR). In the present work, we examined whether repeated WD-PR alters hypothalamic transcripts related to the brain renin-angiotensin system (RAS) and apelin system in male normotensive Holtzman rats (HTZ). We also examined whether the sodium intake of a strain with genetically inherited high expression of the brain RAS, the spontaneously hypertensive rat (SHR), responds differently than HTZ to repeated WD-PR. We found that repeated WD-PR, besides enhancing spontaneous and induced 0.3 M NaCl intake, increased the hypothalamic expression of angiotensinogen, aminopeptidase N, and apelin receptor transcripts (43%, 60%, and 159%, respectively) in HTZ at the end of the third WD-PR. Repeated WD-PR did not change the daily spontaneous 0.3 M NaCl intake and barely changed the need-induced 0.3 M NaCl intake of SHR. The same treatment consistently enhanced spontaneous daily 0.3 M NaCl intake in the normotensive Wistar-Kyoto rats. The results show that repeated WD-PR produces alterations in hypothalamic transcripts and also sensitizes sodium appetite in HTZ. They suggest an association between the components of hypothalamic RAS and the apelin system, with neural and behavioral plasticity produced by repeated episodes of WD-PR in a normotensive strain. The results also indicate that the inherited hyperactive brain RAS is not a guarantee for sensitization of sodium intake in the male adult SHR exposed to repeated WD-PR.

Onset of glomerular hypertension with aging precedes injury in the spontaneously hypertensive rat

2000 ◽  
Vol 278 (5) ◽  
pp. F839-F846 ◽  
Author(s):  
Evelyn M. Tolbert ◽  
Joseph Weisstuch ◽  
Helen D. Feiner ◽  
Lance D. Dworkin
Keyword(s):  
Spontaneously Hypertensive Rat ◽  
Renin Angiotensin System ◽  
Systemic Blood Pressure ◽  
Renal Hemodynamics ◽  
Glomerular Sclerosis ◽  
Compensatory Response ◽  
Spontaneously Hypertensive ◽  
Glomerular Hypertension ◽  
Wistar Kyoto ◽  
Endogenous Activity

The changes in renal hemodynamics that develop with aging in spontaneously hypertensive rats (SHR) were examined. Micropuncture studies revealed that glomerular capillary pressure was elevated in SHR at 9 mo of age compared with 3-mo-old SHR and 9-mo-old normotensive Wistar-Kyoto rats. Glomerular hypertension developed because of a small increase in systemic blood pressure and a decline in preglomerular vascular resistance, allowing transmission of elevated systemic pressure to the glomerular capillaries. The hemodynamic alterations were not a compensatory response to injury, inasmuch as vascular and glomerular morphology were normal in 9-mo-old SHR. To determine the mechanism of these changes, the activity of several vasoactive systems was examined. Similar changes in renal hemodynamics were observed in young and old SHR after blockade of nitric oxide production and after intravenous administration of endothelin. However, ANG II produced a proportionally greater reduction in glomerular filtration rate than renal blood flow in older SHR. These data suggest that reduced endogenous activity of the renin-angiotensin system leads to glomerular hypertension in aging SHR. Late development of glomerular hypertension may contribute to the subsequent appearance of glomerular sclerosis and progressive renal failure in these rats.

Hypothalamic angiotensin receptor subtypes in normotensive and hypertensive rats

1998 ◽  
Vol 275 (2) ◽  
pp. H703-H709 ◽  
Author(s):  
N. L. Han ◽  
M. K. Sim
Keyword(s):  
Angiotensin Ii ◽  
Spontaneously Hypertensive Rat ◽  
Renin Angiotensin System ◽  
Receptor Subtypes ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
Angiotensin Iii ◽  
Displacement Experiments ◽  
Wistar Kyoto Rat ◽  
Wistar Kyoto

The binding of125I-labeled [Sar1,Ile8]angiotensin II to the hypothalamic membranes of the normotensive Wistar-Kyoto rat (WKY) and the spontaneously hypertensive rat (SHR) was studied. Displacement experiments with four centrally active angiotensins, losartan, and PD-123319 confirm the known existence of angiotensin AT1 and AT2 receptors in the rat hypothalamus. The values of the inhibitory constants for angiotensin II and PD-123319 in the SHR were significantly lower than the corresponding values in the WKY, indicating the possible existence of high-affinity hypothalamic AT1 and AT2 receptors for the two ligands in the SHR. The angiotensin AT1receptor was further separated into a 5′-guanylyl imidodiphosphate-sensitive and -nonsensitive subtype, indicating that one of the subtypes is G protein coupled. The SHR has significantly higher numbers of measurable AT1-receptor subtypes as well as AT2 receptor subtypes. The former data support the findings of other investigators showing that the hypothalamus of the SHR expressed more AT1A and AT1B mRNAs than that of the normotensive rat. Des-Asp1-angiotensin I, which is known to attenuate the central pressor action of angiotensin II and angiotensin III, acts on both the AT1 and AT2 receptors, although it has a higher affinity for the AT1receptors. The overall increase in the number of AT1 and AT2 receptors in the SHR is in line with the contention that the brain of the hypertensive rat, compared with that of the WKY, has a hyperactive renin-angiotensin system.

Upregulation of endothelin-1 binding in tissues of salt-loaded stroke-prone spontaneously hypertensive rats

2002 ◽  
Vol 80 (5) ◽  
pp. 470-474 ◽  
Author(s):  
Paula Savage ◽  
Arco Y Jeng
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Spontaneously Hypertensive Rat ◽  
Similar Proportion ◽  
Receptor Subtypes ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Endothelin 1 ◽  
Wistar Kyoto ◽  
Kidney Liver ◽  
The Brain

Upon maintained on a 1% NaCl drinking solution beginning at 7 weeks of age, the stroke-prone spontaneously hypertensive rat (SHRsp) developed severe hypertension and stroke; most died by 16 weeks. The mechanism by which these diseases evolve remains unclear. Endothelin-1 (ET-1) is a potent, peptidic vasoconstrictor and is implicated in the pathogenesis of various cardiovascular, renal, and central nervous system diseases. The purpose of the present study was to compare the binding of [125I]ET-1 to the brain, heart, kidney, liver, and spleen membrane preparations of 16-week-old SHRsp and age-matched normotensive Wistar–Kyoto rats (WKY). The KD values for [125I]ET-1 binding to the corresponding tissues of the two strains were not significantly different, except in the brain (SHRsp: 17 ± 1 pM; WKY: 24 ± 1 pM). In contrast, the Bmax values measured in the brain, heart, kidney, and liver of SHRsp were 1.5- to 2.1-fold greater than those of their WKY counterparts. Competition of [125I]ET-1 binding to the membrane preparations by the specific ETA receptor antagonist BQ-123 or the specific ETB receptor agonist sarafotoxin S6c revealed a similar proportion of ETA and ETB receptor subtypes in the corresponding tissues of the two rat strains. These results indicate that ET-1 binding is upregulated in SHRsp and suggest that ET-1 may play a pathophysiological role in this animal model of genetic hypertension.Key words: ETA receptor, ETB receptor, BQ-123, sarafotoxin 6C, stroke-prone spontaneously hypertensive rats.

Sodium intake is increased by social stress and the Y chromosome and reduced by clonidine

2000 ◽  
Vol 278 (2) ◽  
pp. R407-R412 ◽  
Author(s):  
Daniel Ely ◽  
Michael Herman ◽  
Lawrence Ely ◽  
Linda Barrett ◽  
Amy Milsted
Keyword(s):  
Y Chromosome ◽  
Social Stress ◽  
Spontaneously Hypertensive Rat ◽  
Sodium Intake ◽  
Gender Effect ◽  
Female Rats ◽  
Rat Strains ◽  
Spontaneously Hypertensive ◽  
Stress Effects ◽  
Wistar Kyoto

The objectives were to determine 1) if female rats have higher Na intake than males and if social stress increases Na intake, 2) if the sympathetic nervous system (SNS) mediates the stress effects and the gender effect, and 3) if the Y chromosome (Yc) from a hypertensive father increases Na intake. Four rat strains ( n = 10/group) of both sexes were used: 1) Wistar Kyoto normotensive (WKY), 2) an F16 backcross with a Yc from a hypertensive father (SHR/y), 3) spontaneously hypertensive rat (SHR), and 4) an F16 backcross with a Yc from a normotensive father (SHR/a). Females showed greater baseline Na intake than males (hypertensive strains), intruder stress increased Na intake, and clonidine decreased Na intake, but not in WKY or SHR females. SHR/y males had higher baseline Na intake compared with WKY males. In conclusion, the higher Na intake in females during baseline and stress was partially mediated through the SNS in hypertensive strains and the SHR Yc was partially responsible for the increased Na intake in SHR/y and SHR males compared with WKY.

Reversal of hypertension by angiotensin II type 1 receptor antisense gene therapy in the adult SHR

1999 ◽  
Vol 277 (3) ◽  
pp. H1260-H1264 ◽  
Author(s):  
Michael J. Katovich ◽  
Craig H. Gelband ◽  
Phyllis Reaves ◽  
Hong-Wei Wang ◽  
Mohan K. Raizada
Keyword(s):  
Gene Therapy ◽  
Angiotensin Ii ◽  
Vascular Reactivity ◽  
Spontaneously Hypertensive Rat ◽  
Renin Angiotensin System ◽  
Antisense Gene ◽  
Spontaneously Hypertensive ◽  
Gene Therapy Approach ◽  
Wistar Kyoto

Pharmacological blockade of the renin-angiotensin system in both hypertensive patients and animal models such as the spontaneously hypertensive rat (SHR) effectively reduces blood pressure (BP). Recent studies have established that virally mediated delivery (vector LNSV) of antisense to the angiotensin II type 1 receptor (LNSV-AT1R-AS) will attenuate or abolish the development of hypertension in the SHR. However, the effectiveness of this gene therapy approach to reduce high BP once it is established in the adult has not been ascertained. In this study, we investigated the hypothesis that viral delivery of AT1R-AS into the adult SHR will reduce BP and reverse the vascular reactivity associated with the hypertension. Intracardiac injection of virus particles containing LNSV-AT1R-AS into adult SHR resulted in a 30- to 60-mmHg reduction in BP that was maintained for up to 36 days compared with SHR treated with virus alone (LNSV without antisense). Measurement of renal resistance arteriolar reactivity demonstrated a leftward shift in the KCl and phenylephrine concentration-response relationships and an impaired endothelium-dependent relaxation to ACh in LNSV-treated SHR compared with control Wistar-Kyoto rats. These vascular alterations were reversed in the LNSV-AT1R-AS-treated SHR. Collectively, these data demonstrate that virally mediated gene delivery of AT1R-AS can effectively reduce BP and reverse renovascular pathophysiology associated with the hypertensive state when administered to the adult SHR.

The Rat SA Gene Shows Genotype-Dependent Tissue-Specific Expression

1994 ◽  
Vol 87 (1) ◽  
pp. 1-4 ◽  
Author(s):  
Michael A. Kaiser ◽  
David Lodwick ◽  
Nilesh J. Samani
Keyword(s):  
Spontaneously Hypertensive Rat ◽  
Northern Blotting ◽  
Specific Expression ◽  
Tissue Specific ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
Wistar Kyoto Rat ◽  
Wistar Kyoto ◽  
Kidney Liver ◽  
The Brain

1. SA is a recently identified gene implicated in blood pressure regulation in rodent models of genetic hypertension. In this study we have examined, by Northern blotting, its expression in tissues of the spontaneously hypertensive rat, the Wistar-Kyoto rat and F2 rats, derived from a cross of the spontaneously hypertensive rat with the Wistar-Kyoto rat. 2. We demonstrate that the gene is expressed in a tissue-specific manner. Expression was detected in four sites: kidney, liver, brain and testes. 3. In the kidney and liver expression was higher in the spontaneously hypertensive rat than in the Wistar-Kyoto rat, whereas in the brain and testes the pattern was reversed. 4. In the F2 rats, the levels of SA mRNA in the liver, brain and testes were found to be primarily determined by the genotype at the SA gene locus. 5. The findings suggest the presence of strain-specific cis- and more than one tissue-specific trans-acting factors regulating the expression of the rat SA gene.

Significance of the Brain Renin—Angiotensin System in Spontaneously Hypertensive Rats

1982 ◽  
Vol 63 (s8) ◽  
pp. 159s-161s ◽  
Author(s):  
Jeroen A. D. M. Tonnaer ◽  
Joke J. van Put ◽  
Victor M. Wiegant ◽  
Wybren de Jong
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Spontaneously Hypertensive Rat ◽  
Renin Angiotensin System ◽  
Hypotensive Effect ◽  
Sympathetic Outflow ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
Spontaneously Hypertensive ◽  
Renin Angiotensin ◽  
The Brain

1. The renin inhibitor N-acetyl-pepstatin was infused for 14 days or 5 days into the cerebral ventricular system of young and adult spontaneously hypertensive rats respectively. 2. The blood pressure and heart rate of the young animals was significantly lower as a result of this treatment, whereas the pressure of the adult animals tended to decrease. 3. The mechanism involved in the hypotensive effect of N-acetyl-pepstatin appeared to be independent of the peripheral renin-angiotensin system. The possible involvement of a decreased sympathetic outflow is suggested. 4. The present data indicate that the brain renin-angiotensin system contributes to the development of hypertension in the spontaneously hypertensive rat.

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

2010 ◽  
Vol 298 (5) ◽  
pp. R1298-R1309 ◽  
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.

scholarly journals Increases in plasma trans-EETs and blood pressure reduction in spontaneously hypertensive rats

2011 ◽  
Vol 300 (6) ◽  
pp. H1990-H1996 ◽  
Author(s):  
Houli Jiang ◽  
John Quilley ◽  
Anabel B. Doumad ◽  
Angela G. Zhu ◽  
John R. Falck ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rat ◽  
Blood Pressure Reduction ◽  
Maximal Velocity ◽  
Spontaneously Hypertensive ◽  
Cis And Trans Isomers ◽  
Wistar Kyoto Rat ◽  
Wistar Kyoto ◽  
Cis And Trans ◽  
Cis Isomer

Epoxyeicosatrienoic acids (EETs) are vasodilator, natriuretic, and antiinflammatory lipid mediators. Both cis- and trans-EETs are stored in phospholipids and in red blood cells (RBCs) in the circulation; the maximal velocity ( Vmax) of trans-EET hydrolysis by soluble epoxide hydrolase (sEH) is threefold that of cis-EETs. Because RBCs of the spontaneously hypertensive rat (SHR) exhibit increased sEH activity, a deficiency of trans-EETs in the SHR was hypothesized to increase blood pressure (BP). This prediction was fulfilled, since sEH inhibition with cis-4-[4-(3-adamantan-1-ylureido)cyclohexyloxy]benzoic acid (AUCB; 2 mg·kg−1·day−1 for 7 days) in the SHR reduced mean BP from 176 ± 8 to 153 ± 5 mmHg ( P < 0.05), whereas BP in the control Wistar-Kyoto rat (WKY) was unaffected. Plasma levels of EETs in the SHR were lower than in the age-matched control WKY (16.4 ± 1.6 vs. 26.1 ± 1.8 ng/ml; P < 0.05). The decrease in BP in the SHR treated with AUCB was associated with an increase in plasma EETs, which was mostly accounted for by increasing trans-EET from 4.1 ± 0.2 to 7.9 ± 1.5 ng/ml ( P < 0.05). Consistent with the effect of increased plasma trans-EETs and reduced BP in the SHR, the 14,15- trans-EET was more potent (ED50 10−10 M; maximum dilation 59 ± 15 μm) than the cis-isomer (ED50 10−9 M; maximum dilation 30 ± 11 μm) in relaxing rat preconstricted arcuate arteries. The 11,12-EET cis- and trans-isomers were equipotent dilators as were the 8,9-EET isomers. In summary, inhibition of sEH resulted in a twofold increase in plasma trans-EETs and reduced mean BP in the SHR. The greater vasodilator potency of trans- vs. cis-EETs may contribute to the antihypertensive effects of sEH inhibitors.

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