Temporal relationship between renal cyst development, hypertension and cardiac hypertrophy in a new rat model of autosomal recessive polycystic kidney disease

Jacqueline K. Phillips*, Deborah Hopwood, Rhonda A. Loxley, Kamaljit Ghatora, Jason D. Coombes, Ying Sin Tan, Joanne L. Harrison, Douglas J. McKitrick, Vasyl Holobotvskyy, Leonard F. Arnolda, Gopala K. Rangan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)

Abstract

Background/Methods: We have examined the hypothesis that cyst formation is key in the pathogenesis of cardiovascular disease in a Lewis polycystic kidney (LPK) model of autosomal-recessive polycystic kidney disease (ARPKD), by determining the relationship between cyst development and indices of renal function and cardiovascular disease. Results: In the LPK (n = 35), cysts appear at week 3 (1.1 ± 0.1 mm) increasing to week 24 (2.8 ± 2 mm). Immunostaining for nephron-specific segments indicate cysts develop predominantly from the collecting duct. Cyst formation preceded hypertension (160 ± 22 vs. Lewis control 105 ± 20 mm Hg systolic blood pressure (BP), n = 12) at week 6, elevated creatinine (109 ± 63 vs. 59 ± 6 μmol/l, n = 16) and cardiac mass (0.7 vs. 0.4% bodyweight, n = 15) at week 12, and left ventricular hypertrophy (2,898 ± 207 vs. 1,808 ± 192 μm, n = 14) at week 24 (all p ≤ 0.05). Plasma-renin activity and angiotensin II were reduced in 10- to 12-week LPK (2.2 ± 2.9 vs. Lewis 11.9 ± 4.9 ng/ml/h, and 25.0 ± 19.1 vs. 94.9 ± 64.4 pg/ml, respectively, n = 26, p ≤ 0.05). Ganglionic blockade (hexamethonium 3.3 mg/kg) significantly reduced mean BP in the LPK (52 vs. Lewis 4%, n = 9, p ≤ 0.05). Conclusion: Cyst formation is a key event in the genesis of hypertension while the sympathetic nervous system is important in the maintenance of hypertension in this model of ARPKD.

Original languageEnglish
Pages (from-to)129-144
Number of pages16
JournalKidney and Blood Pressure Research
Volume30
Issue number3
DOIs
Publication statusPublished - Jun 2007
Externally publishedYes

Keywords

  • Autosomal-recessive polycystic kidney disease
  • Cystogenesis
  • Hypertension
  • Immunohistochemistry
  • Left ventricular hypertrophy
  • Renin-angiotensin-aldosterone system
  • Sympathetic nervous system

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