Dietary Protein Source Determines the Degree of Hypertension and Renal Disease in the Dahl Salt-Sensitive Rat

Abstract

Abstract-Previous studies demonstrated that a whole-grain diet attenuated sodium-dependent hypertension and renal disease in Dahl salt-sensitive rats from the colony at the Medical College of Wisconsin (Dahl SS/Mcw rats) compared with rats maintained on a purified AIN-76A diet. The present experiments determined which component(s) of the grain diet prevented renal and cardiovascular disease. Male SS/Mcw rats were maintained on isocaloric diets identical to AIN-76A, except the source of protein (wheat gluten for casein), carbohydrate (wheat flour for sucrose), or fat (soybean oil for corn oil) was substituted in separate diets. Rats were maintained on the different diets from weaning and studied after 3 weeks on a high-salt (4.0% NaCl) diet. Substitution of the carbohydrate in the diet did not affect body weight, arterial pressure, or renal disease. Replacement of casein with wheat gluten significantly reduced body weight (258Ϯ7 versus 353Ϯ3 grams), mean arterial pressure (133Ϯ2 versus 153Ϯ2 mm Hg), and albumin excretion (9Ϯ1 versus 50Ϯ7 mg/d) to levels of rats fed the whole-grain diet (nϭ7 to 16/group). Replacement of the fat in the diet increased arterial pressure without affecting body weight or albumin excretion. Key Words: hypertension, sodium-dependent Ⅲ rats Ⅲ blood pressure Ⅲ diet T he composition and quantity of dietary nutrients can have profound effects on arterial blood pressure. In humans, increased consumption of food containing cholesterol, saturated fats, or carbohydrates is associated with an elevation of arterial blood pressure, whereas a high-protein diet is linked to a decrease in blood pressure. [1][2][3][4] Experimental studies have also examined the influence of changes in dietary protein, fat, and carbohydrates on arterial blood pressure in animal models. The development of hypertension is accelerated in genetic models of hypertension depending on the source and composition of dietary protein, 5 carbohydrates, 6 -9 and fat. 9,10 These clinical and experimental results indicate that different components of the diet, independent of sodium chloride content, can have a profound influence on the long-term level of arterial blood pressure.Studies from our laboratory demonstrated that sodiumsensitive changes in blood pressure and kidney disease in inbred Dahl salt-sensitive rats from the colony at the Medical College of Wisconsin (Dahl SS/Mcw rats) were modified depending on the chow fed to the rats. Rats fed chow formulated following the guidelines established by the American Institute of Nutrition in 1976 (AIN-76A) 11,12 had a greater degree of sodium-dependent hypertension and renal disease in comparison to rats fed a diet derived largely from grain products. 13 The AIN-76A and the grain diet (Teklad 3075S) are composed of approximately the same percentage of protein, carbohydrates, and fat. Differences between the 2 diets, however, include the source of protein (casein in the AIN-76A versus corn and wheat protein in the grain diet), carbohydrates (sucrose and corn starch in AIN-76A versus cor...

Immune Suppression Attenuates Hypertension and Renal Disease in the Dahl Salt-Sensitive Rat

“…Consistent with previous reports in the Dahl SS/Mcw rat, 16,17 both glomerular damage (blue fibrotic tissue and collapsed capillary structure) To assess the effectiveness of MMF in the kidney, immunoblotting experiments were performed to quantify the expression of CD5, CD25, ED-1, and osteopontin in protein homogenates obtained from the renal cortex of rats treated with vehicle or MMF (Figure 7; nϭ5 per group). Systemic treatment with MMF resulted in a significant decrease in each marker in the renal cortex of the Dahl SS rats when compared with vehicle-treated Dahl SS rats, indicating that systemic MMF treatment successfully suppressed immune cell infiltration in the kidneys of the SS/Mcw rats.…”

“…This maneuver, which we have used previously to evaluate sodium sensitivity of arterial blood pressure in experimental animals, 16,17 is an adaptation of a method used to assess sodium sensitivity of blood pressure in patients. 18 After 1 day on the 0.4% NaCl diet, an overnight urine collection (from 4:00 PM to 8:00 AM) was obtained to quantify sodium and creatinine excretion.…”

“…Individual glomeruli (30 to 40 per rat) were evaluated using the semiquantitative index method of Raij et al 20 ; glomeruli were scored from 0 (best) to 4 (worst) on the basis of glomerulosclerosis and mesangial expansion as we described previously. 16,17 The percentage of the outer medullary tissue containing blocked tubules filled with protein was quantified by determining the proportion of red-stained structures in this region using Metamorph Image Analysis software (version 4.6, Universal Imaging Systems Corp) as we described previously. 16,17 The grading of glomerular and medullary damage was performed in a blinded manner.…”

“…16,17 The percentage of the outer medullary tissue containing blocked tubules filled with protein was quantified by determining the proportion of red-stained structures in this region using Metamorph Image Analysis software (version 4.6, Universal Imaging Systems Corp) as we described previously. 16,17 The grading of glomerular and medullary damage was performed in a blinded manner. The rats were fed 0.4% NaCl chow from weaning until 9 weeks of age.…”

Mapping genetic determinants of kidney damage in rat models

“…16,38,43,48,53,54 The magnitude of albuminuria is not only enhanced by high-salt intake but also modified by the composition of dietary protein intake. 55,56 In addition, the rats develop left ventricular hypertrophy and fibrosis, 47,49,51,57 hyperlipidemia 46,51 and insulin resistance. [58][59][60] Cosegregation and linkage analyses Different studies addressed the genetics of albuminuria in SS rats under either normal/low-salt or high-salt diet.…”