Induction of albuminuria and kidney damage in SHR by transfer of chromosome 8 from Munich Wistar Frömter rats

2012 ◽  
Vol 44 (1) ◽  
pp. 110-116 ◽  
Author(s):  
Angela Schulz ◽  
Sabrina Schütten-Faber ◽  
Nicole van Es ◽  
Johannes Unland ◽  
Leonard Schulte ◽  
...  
Keyword(s):  
Structural Changes ◽  
Spontaneously Hypertensive Rat ◽  
Damage Index ◽  
Young Male ◽  
Kidney Damage ◽  
Chromosome 8 ◽  
Spontaneously Hypertensive ◽  
Rat Strain ◽  
Trait Locus

Inbred Munich Wistar Frömter [MWF/FubRkb (RGD:724569), MWF] rats develop progressive albuminuria with age that is under polygenetic influence. We previously identified a major albuminuria quantitative trait locus (QTL) on rat chromosome (RNO)8 in MWF. To test the independent role of QTL(s) for albuminuria development on RNO8, we generated a consomic SHR-Chr 8MWF/Rkb (SHR-8MWF) strain by transferring RNO8 from MWF into the albuminuria-resistant background of the spontaneously hypertensive rat [SHR/FubRkb (RGD:631696; SHR)]. Young male MWF, SHR, and SHR-8MWF were sham-operated or unilaterally nephrectomized (Nx) at 6 wk and followed up to 24 wk of age, respectively. Systolic blood pressure was significantly lower in SHR-8MWF Sham compared with SHR Sham (−19.4 mmHg, P = 0.03) at 24 wk. In contrast, transfer of MWF-RNO8 into SHR induced a significant elevation of urinary albumin excretion (UAE) between weeks 12 and 24 in SHR-8MWF compared with SHR Sham animals ( P < 0.0001, respectively). Nx resulted in a significant increase in UAE in both strains during follow-up ( P < 0.0001, respectively), with significant higher values in SHR-8MWF compared with SHR ( P < 0.005, respectively). Renal structural changes as determined by glomerulosclerosis (GSI) and tubulointerstitial damage index (TDI) were significantly higher in consomic animals either at Sham (TDI) or Nx (GSI) conditions ( P < 0.05, respectively). These data confirm the independent role of MWF QTL(s) on RNO8 for both albuminuria and structural kidney damage. Moreover, this study shows for the first time the induction of albuminuria by transferring one or more albuminuria QTL into a resistant recipient background in a consomic rat strain.

Nephron deficit is not required for progressive proteinuria development in the Munich Wistar Frömter rat

2008 ◽  
Vol 35 (1) ◽  
pp. 30-35 ◽  
Author(s):  
Angela Schulz ◽  
Jonna Hänsch ◽  
Kristina Kuhn ◽  
Maria Schlesener ◽  
Peter Kossmehl ◽  
...  
Keyword(s):  
Mild Hypertension ◽  
Genetic Model ◽  
Fold Increase ◽  
Chromosome 8 ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Trait Locus ◽  
Consomic Strain ◽  
Nephron Deficit

The Munich Wistar Frömter (MWF) rat represents a genetic model with an inherited nephron deficit and exhibits mild hypertension and progressive albuminuria, which is more pronounced in males than females. Previously, we demonstrated in a consomic strain that replacement of a quantitative trait locus on chromosome 6 normalized the nephron deficit and suppressed albuminuria development, suggesting a link between the two findings. Here we tested the role of a second major locus linked to albuminuria in MWF on chromosome 8 and generated the consomic strain MWF-8SHR by transfer of chromosome 8 from spontaneously hypertensive rats (SHR) into MWF. The early onset of albuminuria at 8 wk of age in MWF (>50-fold increase compared with SHR) was significantly suppressed in consomic animals, and the development of marked proteinuria at 32 wk significantly diminished. Total nephron number in consomic rats (23,771 ± 1,352) and MWF (27,028 ± 1,322) were similar and significantly lower (−36%) compared with SHR (36,979 ± 1,352, P < 0.0001). The development of mild albuminuria in female MWF was also significantly diminished in MWF-8SHR. Thus, the development of overt and mild albuminuria in male and female MWF rats is not a mandatory consequence of the inherited nephron deficit. The locus on chromosome 8 appears of interest, because its exchange between MWF and SHR protects against the development of albuminuria in MWF-8SHR animals despite their inherited nephron deficit and higher systolic blood pressure.

Role of adenosine in noradrenergic neurotransmission in spontaneously hypertensive rats

1987 ◽  
Vol 253 (4) ◽  
pp. H909-H918 ◽  
Author(s):  
E. K. Jackson
Keyword(s):  
Plasma Levels ◽  
Spontaneously Hypertensive Rat ◽  
Base Line ◽  
Inhibitory Effects ◽  
Spontaneously Hypertensive ◽  
Vascular Responses ◽  
Rat Mesentery ◽  
Wistar Kyoto

The purpose of this study was to compare the in vivo role of adenosine as a modulator of noradrenergic neurotransmission in the spontaneously hypertensive rat (SHR) and Wistar-Kyoto control rat (WKY). In the in situ blood-perfused rat mesentery, vascular responses to periarterial (sympathetic) nerve stimulation (PNS) and to exogenous norepinephrine (NE) were enhanced in SHR compared with WKY. In both SHR and WKY, vascular responses to PNS were more sensitive to inhibition by adenosine than were responses to NE. At matched base-line vascular responses, compared with WKY, SHR were less sensitive to the inhibitory effects of adenosine on vascular responses to PNS, but SHR and WKY were equally sensitive with respect to adenosine-induced inhibition of responses to NE. Antagonism of adenosine receptors with 1,3-dipropyl-8-p-sulfophenylxanthine shifted the dose-response curve to exogenous adenosine sixfold to the right yet did not influence vascular responses to PNS or NE in either SHR or WKY. Furthermore, PNS did not alter either arterial or mesenteric venous plasma levels of adenosine in SHR or WKY, and plasma levels of adenosine in both strains were always lower than the calculated threshold level required to attenuate neurotransmission. It is concluded that in vivo 1) exogenous adenosine interferes with noradrenergic neurotransmission in both SHR and WKY; 2) SHR are less sensitive to the inhibitory effects of exogenous adenosine on noradrenergic neurotransmission than are WKY; 3) endogenous adenosine does not play a role in modulating neurotransmission in either strain under the conditions of this study; and 4) enhanced noradrenergic neurotransmission in the SHR is not due to defective modulation of neurotransmission by adenosine.

Cardiomyocyte function associated with hyperactivity and/or hypertension in genetic models of LV hypertrophy

2006 ◽  
Vol 290 (1) ◽  
pp. H463-H473 ◽  
Author(s):  
Bradley M. Palmer ◽  
Zengyi Chen ◽  
Richard R. Lachapelle ◽  
Edith D. Hendley ◽  
Martin M. LeWinter
Keyword(s):  
Spontaneously Hypertensive Rat ◽  
Left Ventricular ◽  
Adult Males ◽  
Compensatory Response ◽  
Spontaneously Hypertensive ◽  
Hypertrophic Response ◽  
Rat Strain ◽  
Males And Females ◽  
Sarcomere Dynamics ◽  
Wistar Kyoto

We examined cardiomyocyte intracellular calcium ([Ca2+]i) dynamics and sarcomere shortening dynamics in genetic rat models of left ventricular (LV) hypertrophy associated with or without hypertension (HT) and with or without hyperactive (HA) behavior. Previous selective breeding of the spontaneously hypertensive rat (SHR) strain, which is HA and HT, with the Wistar-Kyoto (WKY) rat strain, which is not hyperactive (NA) and not hypertensive (NT), has led to two unique strains: the WKHA strain, selected for HA and NT, and the WKHT strain, selected for NA and HT. Cardiomyocytes were isolated from young adult males and females of each strain, paced at 2, 3, and 4 Hz in 1.2 mM external Ca2+ concentration at 37°C, and cardiomyocyte [Ca2+]i and sarcomere dynamics were recorded simultaneously. Under these conditions, LV cardiomyocyte systolic and diastolic [Ca2+]i dynamics and diastolic sarcomere dynamics in the WKHT were significantly enhanced compared with WKY controls, suggesting an underlying LV hypertrophic response that successfully compensated for HT in the absence of HA. LV cardiomyocyte [Ca2+]i dynamics in the WKHA and SHR were strikingly similar to each other and only slightly reduced compared with WKY. LV cardiomyocyte systolic and diastolic sarcomere dynamics, on the other hand, were significantly reduced in the SHR compare with WKHA and more so in male than in female SHR. We conclude from these data that HT alone is an insufficient descriptor of the cause of LV hypertrophy and diminished LV cardiomyocyte function in the SHR rat. These data further suggest that HA (augmented by male sex) in the SHR may interact with the HT state to initiate impaired cardiomyocyte function and thereby inhibit or undermine an otherwise compensatory response that may occur with HT in the absence of HA.

scholarly journals Distribution and role of angiotensin II receptor in the brain of spontaneously hypertensive rat.

1980 ◽  
Vol 44 (5) ◽  
pp. 403-408 ◽  
Author(s):  
KENJI MIZUNO ◽  
SHUICHI SHIGETOMI ◽  
JUN-ICHIROH MATSUI ◽  
SOITSU FUKUSHI
Keyword(s):  
Angiotensin Ii ◽  
Spontaneously Hypertensive Rat ◽  
Angiotensin Ii Receptor ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
The Brain

Phosphorylation of RyR2 and shortening of RyR2 cluster spacing in spontaneously hypertensive rat with heart failure

2007 ◽  
Vol 293 (4) ◽  
pp. H2409-H2417 ◽  
Author(s):  
Ye Chen-Izu ◽  
Christopher W. Ward ◽  
Wayne Stark ◽  
Tamas Banyasz ◽  
Marius P. Sumandea ◽  
...  
Keyword(s):  
Heart Failure ◽  
Spontaneously Hypertensive Rat ◽  
Model Simulation ◽  
Quantitative Model ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
Distinct Disease ◽  
Intracellular Ca ◽  
Disease Stages

As a critical step toward understanding the role of abnormal intracellular Ca2+ release via the ryanodine receptor (RyR2) during the development of hypertension-induced cardiac hypertrophy and heart failure, this study examines two questions: 1) At what stage, if ever, in the development of hypertrophy and heart failure is RyR2 hyperphosphorylated at Ser2808? 2) Does the spatial distribution of RyR2 clusters change in failing hearts? Using a newly developed semiquantitative immunohistochemistry method and Western blotting, we measured phosphorylation of RyR2 at Ser2808 in the spontaneously hypertensive rat (SHR) at four distinct disease stages. A major finding is that hyperphosphorylation of RyR2 at Ser2808 occurred only at late-stage heart failure in SHR, but not in age-matched controls. Furthermore, the spacing between RyR2 clusters was shortened in failing hearts, as predicted by quantitative model simulation to increase spontaneous Ca2+ wave generation and arrhythmias.

Age-dependent regulation of vasopressin V1a receptors in preglomerular vessels from the spontaneously hypertensive rat

2004 ◽  
Vol 286 (5) ◽  
pp. F997-F1003 ◽  
Author(s):  
Øyvind B. Vågnes ◽  
Frank H. Hansen ◽  
Rolf E. F. Christiansen ◽  
Camilla Gjerstad ◽  
Bjarne M. Iversen
Keyword(s):  
Spontaneously Hypertensive Rat ◽  
Mrna Level ◽  
Cytosolic Calcium ◽  
Receptor Expression ◽  
Receptor Protein ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Renal Vascular ◽  
Insight Into

Experiments were performed to get insight into the role of AVP receptor V1a regulation with age, i.e., during development and maintenance of high blood pressure. Previous studies showed an increased gene expression and renal vascular response to AVP in young spontaneously hypertensive rats (SHR). The age regulation of the V1a receptor was examined in preglomerular vessels from 5-, 10-, 20-, and 70-wk-old SHR using normotensive Wistar-Kyoto rats (WKY) as controls. Real-time PCR and ligand binding were used for analysis of receptor expression, and the change in cytosolic calcium concentration during stimulation of isolated preglomerular vessels with AVP was studied. Studies showed an increase of the V1a receptor protein and mRNA from 5-and 10-wk-old SHR compared with vessels from 20- and 70-wk-old SHR. In 5-wk-old SHR receptor density was 84 ± 13 fmol/mg protein, and 38 ± 11 fmol/mg protein in 70-wk-old SHR ( P < 0.05). mRNA in the 5- and 70-wk-old SHR was 15,854 ± 629 and 3,181 ± 224 V1a mRNA/108 18S ribosomal RNA, respectively ( P < 0.001). Values from WKY at all ages were similar to 20- and 70-wk-old SHR. During stimulation with AVP, the change in cytosolic calcium in vessels from 5-wk-old SHR increased 234 ± 59 nM, whereas the increase was 89 ± 9 nM in 70-wk-old SHR ( P = 0.03). These results indicate that the V1a receptor is increased at protein and mRNA level during development of hypertension in SHR but is normalized when hypertension is established.

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