Interactions of hypercholesterolemia and hypertension in initiation of glomerular injury

Jonathan P. Tolins, Bradford G. Stone, Leopoldo Raij

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


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 hypercholeslerolemia 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 < 0.05 vs. DS and DSC). Cholesterol fed rats developed marked and equivalent hypercholesterolemia compared Io controls (DS vs. DSC, 71 ± 3 vs. 289 ± 91 mg/dl, P < 0.05; DR vs. DRC, 52 ± 2 vs. 327 ± 54 mg/dl, P < 0.05). Hypertensive rats (DS, DSC) developed worse proteinuria and glomerular injury than normotensive rats (DR, DRC), but hypercholesterolemia exacerbated proteinuria and giomerulosclerosis only in DSC and not in DRC. Proteinuria significantly correlated with serum cholesterol in hypertensive rats (DS, DSC, P < 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.

Original languageEnglish (US)
Pages (from-to)1254-1261
Number of pages8
JournalKidney international
Issue number5
StatePublished - May 1992

ASJC Scopus subject areas

  • Nephrology


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