Interactions of hypercholesterolemia and hypertension in initiation of glomerular injury.
In the Dahl S rat (DS), salt induces systemic and glomerular capillary hypertension associated with progressive glomerulosclerosis, while Dahl R rats (DR) remain normotensive, without glomerular abnormalities. Studies in experimental models have suggested that hypercholesterolemia may play a role in the development of glomerulosclerosis; however, it is unclear whether hypercholesterolemia alone, in the absence of hypertension, can initiate injury. To answer this question we induced hypercholesterolemia in salt-supplemented DS (DSC) and DR (DRC) by feeding a high cholesterol (4%) chow. Control rats (DS, DR) received high-salt, normal cholesterol chow. After eight weeks, DS and DSC developed equivalent hypertension (161 +/- 3 vs. 153 +/- 3 mm Hg, respectively, P = NS), while DR and DRC remained normotensive (138 +/- 5 vs. 131 +/- 5 mm Hg, P = NS; P less than 0.05 vs. DS and DSC). Cholesterol fed rats developed marked and equivalent hypercholesterolemia compared to controls (DS vs. DSC, 71 +/- 3 vs. 289 +/- 91 mg/dl, P less than 0.05; DR vs. DRC, 52 +/- 2 vs. 327 +/- 54 mg/dl, P less than 0.05). Hypertensive rats (DS, DSC) developed worse proteinuria and glomerular injury than normotensive rats (DR, DRC), but hypercholesterolemia exacerbated proteinuria and glomerulosclerosis only in DSC and not in DRC. Proteinuria significantly correlated with serum cholesterol in hypertensive rats (DS, DSC, P less than 0.05), but not normotensive rats (DR, DRC, P = NS). Furthermore, DSC had increased renal vascular resistance compared to DS, while no differences were found between DRC and DR. Thus, in the Dahl rat, hypercholesterolemia alone does not initiate glomerular injury. In this model, hypercholesterolemia is a pathogenetic factor in glomerular injury only when it coexists with systemic hypertension.
Tolins
J P
JP
Veterans Affairs Medical Center, Minneapolis, Minnesota.
Stone
B G
BG
Raij
L
L
D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D006937:Hypercholesterolemia / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D006973:Hypertension / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000293:injuries*; D011507:Proteinuria / Q000209:etiology; D051381:Rats; D012079:Renal Circulation; D012965:Sodium Chloride / Q000008:administration & dosage
D012965:Sodium Chloride