Effect of repeated novel stressors on depressive behavior and brain norepinephrine receptor system in Sprague-Dawley and Wistar Kyoto (WKY) rats

We investigated kallikrein-binding protein (KBP) mRNA distribution in the kidney of Sprague-Dawley (SD) rats, spontaneously hypertensive rats (SHR), and Wistar-Kyoto strain (WKY) rats. Northern blot analysis revealed that KBP mRNA was located mainly in the medulla and with lower amounts in SHR than in WKY rats. KBP mRNA in microdissected nephron segments was detected by reverse transcription and polymerase chain reaction (RT-PCR) followed by Southern blot analysis. In SD rats, the most abundant signals were consistently found in inner medullary collecting duct (IMCD), with small amounts in outer medullary collecting duct, proximal convoluted tubule, and glomerulus. No signals were found in connecting tubule and cortical collecting duct. The nephron distribution of KBP mRNA was similar in WKY and SD rats. Only a small amount of signal was found, however, in IMCD of SHR. In conclusion, 1) KBP mRNA was predominantly distributed in the medullary segments of the distal nephron, downstream from the known kallikrein activity site in the collecting duct, and 2) KBP mRNA expression was significantly decreased in the kidney of SHR.

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Long-term captopril treatment restores natriuresis after carotid baroreceptor activation in the SHR

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1997.273.1.r70 ◽

1997 ◽

Vol 273 (1) ◽

pp. R70-R79

Author(s):

J. P. Valentin ◽

S. A. Mazbar ◽

M. H. Humphreys

Keyword(s):

Renal Plasma Flow ◽

Renal Nerves ◽

Sprague Dawley ◽

Wky Rats ◽

Sprague Dawley Rats ◽

Long Term Treatment ◽

Bilateral Carotid ◽

Wistar Kyoto ◽

Captopril Treatment

In anesthetized Sprague-Dawley rats, intermittent bilateral carotid artery traction (BilCAT) caused a transient decrease in mean arterial pressure (MAP) of 28 +/- 3 mmHg and led to a progressive increase in sodium excretion (UNaV) that nearly doubled 45-90 min after initiation of the repetitive application of BilCAT (P < 0.001). This natriuresis was accompanied by an increase in glomerular filtration rate (GFR) from 2.70 +/- 0.3 to 3.2 +/- 0.3 ml/min (P < 0.001), no change in renal plasma flow [clearance of p-aminohippurate (PAH)], and an increase in the fractional excretion of lithium. Rats with bilateral renal denervation exhibited neither natriuresis nor an increase in GFR in response to BilCAT despite similar vasodepression caused by the maneuver. Normotensive Wistar-Kyoto (WKY) rats responded to BilCAT like Sprague-Dawley rats, whereas spontaneously hypertensive rats (SHR) exhibited an exaggerated vasodepressor response to BilCAT (-51 +/- 3 mmHg) without increasing either UNaV or GFR. Separate groups of WKY and SHR were treated from 4 wk of age with captopril added to the drinking water at a concentration of 1 g/l. At 12-14 wk, both groups had lower MAP compared with untreated animals. Captopril treatment did not alter either the natriuretic response or the increase in GFR seen in untreated WKY after BilCAT, and the maneuver produced equivalent degrees of vasodepression as in controls. However, treated SHR now responded to BilCAT with increases in both UNaV and GFR that closely resembled the responses seen in Sprague-Dawley and WKY rats. These results suggest that BilCAT produces natriuresis through a pathway dependent on the renal nerves. This pathway does not function in untreated SHR despite similar vasodepression. Long-term treatment with captopril restores this reflex pathway in SHR, lending support to the concept that angiotensin II is critically linked to heightened sympathetic nerve activity and abnormal sodium metabolism in this strain.

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Abstract TP342: Early Erythrolysis in Hematoma After Experimental Hemorrhage

Stroke ◽

10.1161/str.48.suppl_1.tp342 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Ge Dang ◽

Gang Wu ◽

Yiwei Zeng ◽

Ya Hua ◽

Richard F Keep ◽

...

Keyword(s):

Brain Injury ◽

Basal Ganglia ◽

Autologous Blood ◽

Scavenger Receptor ◽

Neuronal Loss ◽

Sprague Dawley ◽

Neuronal Marker ◽

Wky Rats ◽

Wistar Kyoto ◽

T2 Mri

Background: Erythrolysis in the clot after intracerebral hemorrhage (ICH) and the release of hemoglobin causes brain injury but it is unclear when such lysis occurs. The present study examined early erythrolysis in rats. >Methods: Male Sprague-Dawley, spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats had an intracaudate injection of 100μl autologous blood or a needle insertion (sham). All rats had T2 and T2* MRI scanning and brains were used for histology and CD163 (a hemoglobin scavenger receptor) and DARPP-32 (a neuronal marker) immunohistochemistry. Results: There was marked heterogeneity within the hematoma on T2* MRI, with a hyper- or isointense core and a hypointense periphery at days 1 and 3. Hematoxylin and eosin staining in the same animals showed significant erythrolysis in the core with the formation of erythrocyte ghosts. While the periphery of hematoma had erythrocytes with normal profiles, the border of the periphery and the center displayed distorted erythrocytes and areas with ghost erythrocytes. The degree of erythrolysis was correlated with the severity of neuronal loss (marked by DARPP 32) after ICH (r = 0.791, n = 18, p < 0.01). Perihematomal CD163 was increased by day 1 after ICH and may be involved in clearing hemoglobin caused by early hemolysis (303 ± 128 at day 1 and 453 ± 57 cells/mm 2 at day 3, p<0.01). Only a few CD163 positive cells were observed in the ipsilateral basal ganglia of sham controls and in the contralateral basal ganglia of ICH rats. ICH resulted in more severe erythrolysis (e.g. 18.3 ± 4.5 vs. 8.1 ± 5.2 %, p< 0.01 at day 1), neuronal loss (30.0 ± 5.6 vs. 14.1 ± 4.4 %, p<0.05 at day 1), and CD 163 upregulation (p< 0.05) in SHR than in WKY rats. Conclusion: T2*MRI detectable early erythrolysis occurred in the clot after ICH, and activated CD163. Hypertension is associated with enhanced erythrolysis in the hematoma and more brain injury.

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Endorphinergic mechanism in the central cardiovascular and analgesic effects of clonidine

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y87-255 ◽

1987 ◽

Vol 65 (8) ◽

pp. 1624-1632 ◽

Cited By ~ 26

Author(s):

G. Kunos ◽

R. Mosqueda-Garcia ◽

J. A. Mastrianni ◽

F. V. Abbott

Keyword(s):

Receptor Antagonist ◽

Arcuate Nucleus ◽

Monosodium Glutamate ◽

Opiate Receptors ◽

Cardiovascular Effects ◽

Male Rats ◽

Sprague Dawley ◽

Wky Rats ◽

Sd Rats ◽

Wistar Kyoto

In urethane-anesthetized male rats, injection of 5 nmol clonidine into the nucleus of the solitary tract (NTS) causes hypotension and bradycardia. These effects are greater in spontaneously hypertensive rats (SHR) and normotensive Sprague–Dawley (SD) rats than in normotensive Wistar–Kyoto (WKY) rats. The effects of clonidine are stereoselectively inhibited by 100 ng intra-NTS naloxone in SHR and SD but not in WKY rats. In SHR, the effects of clonidine are also inhibited by intra-NTS administration of ICI 174864 (a δ-receptor antagonist) but not by β-funaltrexamine (a μ-receptor antagonist), while in SD rats only the μ- and not the δ-antagonist was effective. Neonatal treatment of SHR with monosodium glutamate (MSG) reduced the β-endorphin content of the arcuate nucleus and the NTS, reduced the cardiovascular effects of clonidine, and abolished their naloxone sensitivity. MSG treatment of newborn WKY reduced the β-endorphin content of the arcuate nucleus but not the NTS and did not affect the responses to clonidine. Measurement of pain sensitivity by the formalin test indicated that clonidine was more potent as an analgesic in SHR and SD than in WKY rats, and its effect was inhibited by naloxone (2 mg/kg i.p.) in the former two strains but not in WKY. It is proposed that a naloxone-sensitive component of the cardiovascular effects of clonidine is due to release of a β-endorphin-like opioid from the NTS, and that this mechanism is present in SHR and SD but not in WKY rats. The opiate receptors mediating the effects of the opioid appear to be of the μ-subtype in SD rats and of the δ-subtype in SHR. The results also support a close relationship between central cardiovascular and pain regulatory mechanisms.

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Plasticity of GABAergic control of hypothalamic presympathetic neurons in hypertension

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00788.2005 ◽

2006 ◽

Vol 290 (3) ◽

pp. H1110-H1119 ◽

Cited By ~ 62

Author(s):

De-Pei Li ◽

Hui-Lin Pan

Keyword(s):

Brain Slices ◽

Functional Change ◽

Ventrolateral Medulla ◽

Sympathetic Outflow ◽

Sprague Dawley ◽

Spontaneously Hypertensive ◽

Wky Rats ◽

Whole Cell Patch Clamp ◽

Output Neurons ◽

Wistar Kyoto

Increased sympathetic outflow contributes to the pathogenesis of hypertension. However, the mechanisms of increased sympathetic drive in hypertension remain unclear. We examined the tonic GABAergic inhibition in control of the excitability of paraventricular (PVN) presympathetic neurons in spontaneously hypertensive rats (SHR) and normotensive controls, including Sprague-Dawley (SD) and Wistar-Kyoto (WKY) rats. Whole cell patch-clamp recordings were performed on retrogradely labeled PVN neurons projecting to the rostral ventrolateral medulla (RVLM) in brain slices. The basal firing rate of PVN neurons was significantly decreased in 13-wk-old SD and WKY rats but increased in 13-wk-old SHR, compared with their respective 6-wk-old controls. The GABAA antagonist bicuculline consistently increased the firing of PVN neurons in normotensive controls. Surprisingly, bicuculline either decreased the firing or had no effect in 59.3% of labeled cells in 13-wk-old SHR. In contrast, the GABAB antagonist CGP-55845 had no effect on the firing of PVN neurons in normotensive controls but significantly increased the firing of 75% of cells studied in 13-wk-old SHR. Furthermore, the evoked GABAA current decreased significantly in labeled PVN neurons of 13-wk-old SHR compared with that in normotensive controls. Both the frequency and amplitude of GABAergic spontaneously inhibitory postsynaptic currents were also reduced in 13-wk-old SHR. This study demonstrates an unexpected functional change in GABAA and GABAB receptors in regulation of the firing activity of PVN-RVLM neurons in SHR. This change in GABAA receptor function and GABAergic inputs to PVN output neurons may contribute to increased sympathetic outflow in hypertension.

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Plasma membrane calcium ATPase isoform expression in cultured rat mesangial cells

AJP Renal Physiology ◽

10.1152/ajprenal.1997.273.1.f76 ◽

1997 ◽

Vol 273 (1) ◽

pp. F76-F83 ◽

Cited By ~ 1

Author(s):

D. Rouse ◽

J. Abramowitz ◽

X. Zhou ◽

T. Kamijo ◽

J. Gonzalez ◽

...

Keyword(s):

Plasma Membrane ◽

Mammalian Cells ◽

Mesangial Cells ◽

Splice Variants ◽

Sprague Dawley ◽

Spontaneously Hypertensive ◽

Homeostatic Process ◽

Calmodulin Binding ◽

Wky Rats ◽

Wistar Kyoto

The maintenance of intracellular ionized calcium (iCa2+) in the submicromolar range is important for mesangial cell (MC) function, and, as in most mammalian cells, plasma membrane Ca(2+)-ATPases (PMCA) play an important role in the homeostatic process. Molecular studies have demonstrated four PMCA isoforms, each with multiple splice variants. The present study examines the expression of PMCA isoforms and calmodulin-binding region splice variants in cultured MC from Sprague-Dawley rats and from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats before and after the onset of hypertension in SHR. Using reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot analyses, we have demonstrated PMCA1, -3, and -4, but not PMCA2, to be present in MC from these rat strains. Splice variant analysis revealed PMCA1a and -1b, PMCA3a, -3b, and -3c, and PMCA4a and -4b to be expressed in MC from all three strains. The relative quantities of PMCA1 and PMCA4 mRNA were not different in age-matched SHR vs. WKY rats, correlating with similar iCa2+ measurements. The expression of all three isoforms declined with age in SHR and WKY.

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Metabolome and microbiome profiling of a stress-sensitive rat model of gut-brain axis dysfunction

Scientific Reports ◽

10.1038/s41598-019-50593-3 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Shalome A. Bassett ◽

Wayne Young ◽

Karl Fraser ◽

Julie E. Dalziel ◽

Jim Webster ◽

...

Keyword(s):

Relative Abundance ◽

Stress Responses ◽

Plasma Lipids ◽

Acute Stress ◽

Physiological Stress ◽

Sprague Dawley ◽

Brain Lipids ◽

Wky Rats ◽

Response To Stress ◽

Wistar Kyoto

Abstract Stress negatively impacts gut and brain health. Individual differences in response to stress have been linked to genetic and environmental factors and more recently, a role for the gut microbiota in the regulation of stress-related changes has been demonstrated. However, the mechanisms by which these factors influence each other are poorly understood, and there are currently no established robust biomarkers of stress susceptibility. To determine the metabolic and microbial signatures underpinning physiological stress responses, we compared stress-sensitive Wistar Kyoto (WKY) rats to the normo-anxious Sprague Dawley (SD) strain. Here we report that acute stress-induced strain-specific changes in brain lipid metabolites were a prominent feature in WKY rats. The relative abundance of Lactococcus correlated with the relative proportions of many brain lipids. In contrast, plasma lipids were significantly elevated in response to stress in SD rats, but not in WKY rats. Supporting these findings, we found that the greatest difference between the SD and WKY microbiomes were the predicted relative abundance of microbial genes involved in lipid and energy metabolism. Our results provide potential insights for developing novel biomarkers of stress vulnerability, some of which appear genotype specific.

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Exacerbated LPS/GalN-Induced Liver Injury in the Stress-Sensitive Wistar Kyoto Rat Is Associated with Changes in the Endocannabinoid System

Molecules ◽

10.3390/molecules25173834 ◽

2020 ◽

Vol 25 (17) ◽

pp. 3834

Author(s):

Marykate Killilea ◽

Daniel M. Kerr ◽

Beth M. Mallard ◽

Michelle Roche ◽

Antony M. Wheatley

Keyword(s):

Liver Injury ◽

Acute Liver Injury ◽

Endocannabinoid System ◽

Hepatic Function ◽

Receptor Expression ◽

Sprague Dawley ◽

Wky Rats ◽

Sd Rats ◽

Rat Strain ◽

Wistar Kyoto

Acute liver injury (ALI) is a highly destructive and potentially life-threatening condition, exacerbated by physical and psychological stress. The endocannabinoid system plays a key role in modulating stress and hepatic function. The aim of this study was to examine the development of acute liver injury in the genetically susceptible stress-sensitive Wistar-Kyoto (WKY) rat compared with normo-stress-sensitive Sprague Dawley (SD) rats, and associated changes in the endocannabinoid system. Administration of the hepatotoxin lipopolysaccharide/D-Galactosamine (LPS/GalN) resulted in marked liver injury in WKY, but not SD rats, with increased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH) plasma levels, significant histopathological changes, increased hepatic pro-inflammatory cytokine expression and caspase-3 activity and expression and reduced Glutathione (GSH) activity. Furthermore, compared to SD controls, WKY rats display increased anandamide and 2-Arachidonoylglycerol levels concurrent with decreased expression of their metabolic enzymes and a decrease in cannabinoid (CB)1 receptor expression following LPS/GalN. CB1 antagonism with AM6545 or CB2 agonism with JWH133 did not alter LPS/GalN-induced liver injury in SD or WKY rats. These findings demonstrate exacerbation of acute liver injury induced by LPS/GalN in a stress-sensitive rat strain, with effects associated with alterations in the hepatic endocannabinoid system. Further studies are required to determine if the endocannabinoid system mediates or modulates the exacerbation of liver injury in this stress-sensitive rat strain.

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Effect of Acute or Repeated Stress on Behavior and Brain Norepinephrine System in Wistar-Kyoto (WKY) Rats

Brain Research Bulletin ◽

10.1016/s0361-9230(97)00140-8 ◽

1997 ◽

Vol 44 (3) ◽

pp. 289-295 ◽

Cited By ~ 51

Author(s):

Hanna M Zafar ◽

William P Paré ◽

Shanaz M Tejani-Butt

Keyword(s):

Brain Norepinephrine ◽

Wky Rats ◽

Repeated Stress ◽

Norepinephrine System ◽

Wistar Kyoto

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High gastrin cell activity and low ghrelin cell activity in high-anxiety Wistar Kyoto rats

Journal of Endocrinology ◽

10.1677/joe-07-0028 ◽

2007 ◽

Vol 193 (2) ◽

pp. 245-250 ◽

Cited By ~ 10

Author(s):

Elin Kristensson ◽

Monika Sundqvist ◽

Rolf Håkanson ◽

Erik Lindström

Keyword(s):

Histidine Decarboxylase ◽

Cell Activity ◽

Sprague Dawley ◽

Plasma Gastrin ◽

High Anxiety ◽

Tissue Samples ◽

Fed State ◽

Wky Rats ◽

Ecl Cell ◽

Wistar Kyoto

Ghrelin is produced by gastric A-like cells and released in response to food deprivation. Interestingly, psychological stress also raises circulating ghrelin levels. This study compared plasma ghrelin levels in Sprague–Dawley (SPD) rats and high-anxiety Wistar Kyoto (WKY) rats. The two strains were also compared with respect to plasma gastrin, a gastric hormone with a pre- and postprandial release pattern opposite to that of ghrelin, and to the activity of the gastrin-dependent, histamine-forming ECL cells in the gastric mucosa. The rats were killed after being freely fed or after an over-night fast. The stomachs were weighed and tissue samples were collected for histological and biochemical analysis. Plasma ghrelin and gastrin levels were determined by RIA. While fasted SPD rats had higher plasma ghrelin levels than fasted WKY rats (P < 0.001), plasma ghrelin did not differ between freely fed rats of the two strains. Gastrin levels were higher in fed WKY rats than in fed SPD rats (P < 0.001). Despite the higher plasma gastrin level, the oxyntic mucosal histidine decarboxylase (HDC) activity (a marker of ECL-cell activity) in fed rats and the mucosal thickness did not differ between the two strains. In a subsequent study, rats were subjected to water-avoidance stress for 60 min, causing plasma gastrin to increase in WKY rats (P < 0.001) but not in SPD rats. In conclusion, high-anxiety WKY rats had lower circulating ghrelin and higher gastrin than SPD rats in both the fasted and fed state, while the ECL-cell activity (HDC activity) was only moderately affected.

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