Interactions of hypercholesterolemia and hypertension in initiation of glomerular injury

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

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

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
Pages (from-to)1254-1261
Number of pages8
JournalKidney International
Volume41
Issue number5
StatePublished - May 1 1992
Externally publishedYes

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Inbred Dahl Rats
Hypercholesterolemia
Hypertension
Wounds and Injuries
Cholesterol
Proteinuria
Salts

ASJC Scopus subject areas

  • Nephrology

Cite this

Interactions of hypercholesterolemia and hypertension in initiation of glomerular injury. / Tolins, Jonathan P.; Stone, Bradford G.; Raij, Leopoldo.

In: Kidney International, Vol. 41, No. 5, 01.05.1992, p. 1254-1261.

Research output: Contribution to journalArticle

Tolins, JP, Stone, BG & Raij, L 1992, 'Interactions of hypercholesterolemia and hypertension in initiation of glomerular injury', Kidney International, vol. 41, no. 5, pp. 1254-1261.
Tolins, Jonathan P. ; Stone, Bradford G. ; Raij, Leopoldo. / Interactions of hypercholesterolemia and hypertension in initiation of glomerular injury. In: Kidney International. 1992 ; Vol. 41, No. 5. pp. 1254-1261.
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