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

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.

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

Physiological Genomics ◽

10.1152/physiolgenomics.00123.2011 ◽

2012 ◽

Vol 44 (1) ◽

pp. 110-116 ◽

Cited By ~ 5

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.

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THE ROLE OF CALCIUM-PROTEIN KINASE C SYSTEMS IN THE REGULATION OF ACETYLCHOLINE RELEASE IN THE CENTRAL NERVOUS SYSTEM OF SPONTANEOUSLY HYPERTENSIVE RATS

Japanese Heart Journal ◽

10.1536/ihj.37.532 ◽

1996 ◽

Vol 37 (4) ◽

pp. 532-532

Author(s):

Kazushi Tsuda ◽

Ichiro Nishio ◽

Yoshiaki Masuyama

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Protein Kinase C ◽

Spontaneously Hypertensive Rats ◽

Acetylcholine Release ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Kinase C ◽

The Central Nervous System

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Role of nuclear proto-oncogenes in the proliferation of aortic smooth muscle cells in spontaneously hypertensive rats

Journal of Hypertension ◽

10.1097/00004872-198900076-00053 ◽

1989 ◽

Vol 7 ◽

pp. S114-115 ◽

Cited By ~ 7

Author(s):

Maryvonne Baudouin-Legros ◽

Jean-Luc Paquet ◽

Gilles Brunelle ◽

Philippe Meyer

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Spontaneously Hypertensive Rats ◽

Muscle Cells ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Aortic Smooth Muscle Cells ◽

Aortic Smooth Muscle

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Increased Pressor Responsiveness to Enkephalin in Spontaneously Hypertensive Rats: The Role of Vasopressin

Clinical Science ◽

10.1042/cs059235s ◽

1980 ◽

Vol 59 (s6) ◽

pp. 235s-237s ◽

Cited By ~ 17

Author(s):

R. W. Rockhold ◽

J. T. Crofton ◽

L. Share

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Pressor Response ◽

Cardiovascular Effects ◽

Hypertensive Rats ◽

Methionine Enkephalin ◽

Spontaneously Hypertensive ◽

Wistar Kyoto Rats ◽

Wistar Kyoto

1. The cardiovascular effects of an enkephalin analogue were examined in spontaneously hypertensive and normotensive Wistar-Kyoto rats. (D-Ala2)-methionine enkephalin caused a biphasic increase in blood pressure and an increase in heart rate after intracerebroventricular injection. 2. The initial pressor response to (D-Ala2)-methionine enkephalin was greater in hypertensive than in normotensive rats. No difference was noted between groups during the secondary pressor response. Heart rate increases paralleled the secondary increase in blood pressure. 3. Naloxone pretreatment abolished the secondary increase in blood pressure and the tachycardia, but did not blunt the initial pressor response in female Wistar-Kyoto rats. 4. Plasma levels of arginine vasopressin were depressed during the plateau phase of the pressor response in hypertensive rats given intracerebroventricular (d-Ala2)-methionine enkephalin. 5. The results suggest that the cardiovascular effects of central enkephalin are not due to vasopressin, but may involve activation of the sympathetic nervous system.

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