Influence of diet and genetics on hypertension and renal disease in Dahl salt-sensitive rats

2004 ◽  
Vol 16 (2) ◽  
pp. 194-203 ◽  
Author(s):  
David L. Mattson ◽  
Mary Pat Kunert ◽  
Mary L. Kaldunski ◽  
Andrew S. Greene ◽  
Richard J. Roman ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Disease ◽  
Arterial Blood Pressure ◽  
Brown Norway ◽  
Tubular Damage ◽  
Norway Rat ◽  
Albumin Excretion ◽  
Protein Excretion ◽  
Arterial Blood ◽  
Brown Norway Rat

Experiments examined the influence of diet and genetics on hypertension and renal disease in inbred Dahl salt-sensitive (SS/Mcw) rats and consomic rats in which chromosomes 16 (SS.BN16) or 18 (SS.BN18) of the normotensive Brown Norway rat were inserted into the genetic background of the SS/Mcw. Dahl SS/Mcw breeders and offspring were randomly placed on a purified AIN-76A diet or a grain-based diet, and male offspring were screened for cardiovascular and renal phenotypes following 3 wk on a 4.0% NaCl diet. High-salt arterial blood pressure (162 ± 5 mmHg, n = 10), urinary protein excretion (147 ± 16 mg/day, n = 14), and albumin excretion (72 ± 9 mg/day, n = 14) were significantly elevated in the Dahl SS/Mcw maintained on the purified diet compared with rats fed the grain-based diet. Rats fed the purified diet also exhibited significantly more renal glomerular and tubular damage than rats fed the grain diet. Moreover, feeding the purified diet to the parents led to a significant increase in blood pressure in the offspring, regardless of offspring diet. Similar dietary effects were observed in SS.BN16 and SS.BN18 rats. In rats fed the purified diet, substitution of chromosomes 16 or 18 led to a significant decrease in arterial blood pressure, albumin excretion, and protein excretion compared with the SS/Mcw. Chromosomal substitution did not, however, affect albumin or protein excretion in the consomic rats compared with the SS/Mcw when the rats were maintained on the grain diet. These data demonstrate a significant influence of diet composition on salt-induced hypertension and renal disease in the Dahl SS/Mcw rat.

scholarly journals Chromosome substitution reveals the genetic basis of Dahl salt-sensitive hypertension and renal disease

2008 ◽  
Vol 295 (3) ◽  
pp. F837-F842 ◽  
Author(s):  
David L. Mattson ◽  
Melinda R. Dwinell ◽  
Andrew S. Greene ◽  
Anne E. Kwitek ◽  
Richard J. Roman ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Disease ◽  
Genetic Basis ◽  
Female Rats ◽  
Male Rats ◽  
Brown Norway ◽  
Chromosome Substitution ◽  
Albumin Excretion ◽  
Arterial Blood ◽  
Salt Sensitive Hypertension

This study examined the genetic basis of hypertension and renal disease in Dahl SS/Mcwi (Dahl Salt-Sensitive) rats using a complete chromosome substitution panel of consomic rats in which each of the 20 autosomes and the X and Y chromosomes were individually transferred from the Brown Norway (BN) rat onto the Dahl SS/Mcwi genetic background. Male and female rats of each of the two parental and 22 consomic strains (10–12 rats/group) were fed a high-salt (8.0% NaCl) diet for 3 wk. Mean arterial blood pressure rose by 60 mmHg and urinary protein and albumin excretion increased 3- and 20-fold, respectively, in male SS/Mcwi rats compared with BN controls. Substitution of chromosomes 1, 5, 7, 8, 13, or 18 from the BN onto the SS/Mcwi background attenuated the development of hypertension, proteinuria, and albuminuria in male rats. In female rats, substitution of chromosomes 1 and 5 also decreased blood pressure, protein excretion, and albumin excretion. These studies also identified several chromosomes in male (6, 11, Y) and female ( 4 , 6 , 11 , 19 , 20 ) rats that reduced albuminuria without altering blood pressure. These data indicate that genes contributing to salt-sensitive hypertension are found on multiple chromosomes of the Dahl SS/Mcwi rat. Furthermore, this consomic rat panel provides a stable genetic platform that can facilitate further gene mapping by either linkage studies or the breeding of congenic and subcongenic rats.

scholarly journals Role of 20-HETE in the antihypertensive effect of transfer of chromosome 5 from Brown Norway to Dahl salt-sensitive rats

2012 ◽  
Vol 302 (10) ◽  
pp. R1209-R1218 ◽  
Author(s):  
Jan M. Williams ◽  
Fan Fan ◽  
Sydney Murphy ◽  
Carlos Schreck ◽  
Jozef Lazar ◽  
...  
Keyword(s):  
Genetic Background ◽  
Chronic Administration ◽  
Brown Norway ◽  
Glomerular Injury ◽  
Chromosome 5 ◽  
Norway Rat ◽  
Protein Excretion ◽  
Elevated Expression ◽  
Brown Norway Rat ◽  
Consomic Strain

This study examined whether substitution of chromosome 5 containing the CYP4A genes from Brown Norway rat onto the Dahl S salt-sensitive (SS) genetic background upregulates the renal production of 20-HETE and attenuates the development of hypertension. The expression of CYP4A protein and the production of 20-HETE were significantly higher in the renal cortex and outer medulla of SS.5BN (chromosome 5-substituted Brown Norway rat) consomic rats fed either a low-salt (LS) or high-salt (HS) diet than that seen in SS rats. The increase in the renal production of 20-HETE in SS.5BN rats was associated with elevated expression of CYP4A2 mRNA. MAP measured by telemetry rose from 117 ± 1 to 183 ± 5 mmHg in SS rats fed a HS diet for 21 days, but only increased to 151 ± 5 mmHg in SS.5BN rats. The pressure-natriuretic and diuretic responses were twofold higher in SS.5BN rats compared with SS rats. Protein excretion rose to 354 ± 17 mg/day in SS rats fed a HS diet for 21 days compared with 205 ± 13 mg/day in the SS.5BN rats, and the degree of glomerular injury was reduced. Baseline glomerular capillary pressure (Pgc) was similar in SS.5BN rats (43 ± 1 mmHg) and Dahl S (44 ± 2 mmHg) rats. However, Pgc increased to 59 ± 3 mmHg in SS rats fed a HS diet for 7 days, while it remained unaltered in SS.5BN rats (43 ± 2 mmHg). Chronic administration of an inhibitor of the synthesis of 20-HETE (HET0016, 10 mg·kg−1·day−1 iv) reversed the antihypertensive phenotype seen in the SS.5BN rats. These findings indicate that the transfer of chromosome 5 from the BN rat onto the SS genetic background increases the renal expression of CYP4A protein and the production of 20-HETE and that 20-HETE contributes to the antihypertensive and renoprotective effects seen in the SS.5BN consomic strain.

scholarly journals STUDIES ON THE MECHANISM OF EXPERIMENTAL PROTEINURIA

1952 ◽  
Vol 96 (6) ◽  
pp. 643-652 ◽  
Author(s):  
Alvin L. Sellers ◽  
Stephen Smith ◽  
Jessie Marmorston ◽  
Howard C. Goodman
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Mean Arterial Blood Pressure ◽  
Plasma Proteins ◽  
Great Increase ◽  
Frozen Sections ◽  
Significant Elevation ◽  
Glomerular Permeability ◽  
Protein Excretion ◽  
Arterial Blood

When renin is administered intramuscularly to the rat, massive proteinuria occurs without a significant elevation of mean arterial blood pressure. The intravenous administration of renin to normal rats results in a great increase in urinary protein excretion. This response to renin is abolished by bilateral adrenalectomy. While the adrenalectomized rat fails to respond to intravenous renin with increased proteinuria, it does exhibit a normal elevation in mean arterial blood pressure. It is concluded that in the rat, the proteinuric property of renin is not related to the ability of this compound to elevate arterial blood pressure. The passage of plasma proteins has been followed through the kidney and into the urine by attaching them to the dye T-1824 (Evan's blue). The intra-peritoneal injection of renin causes a massive, transient proteinuria in the rat. From a study of frozen sections of the kidney of rats whose plasma proteins are labelled with T-1824, it is concluded that the preponderant basis for renin proteinuria is an increase in glomerular permeability.

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