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

Kidney Blood Press Res. 2007;30(3):129-44. doi: 10.1159/000101828. Epub 2007 Apr 19.

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 micromol/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 mum, n = 14) at week 24 (all p < or = 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 < or = 0.05). Ganglionic blockade (hexamethonium 3.3 mg/kg) significantly reduced mean BP in the LPK (52 vs. Lewis 4%, n = 9, p < or = 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Biomarkers / metabolism
  • Creatinine / blood
  • Disease Models, Animal*
  • Female
  • Hypertension, Renal / etiology
  • Hypertension, Renal / genetics
  • Hypertension, Renal / pathology*
  • Hypertrophy, Left Ventricular / etiology
  • Hypertrophy, Left Ventricular / genetics
  • Hypertrophy, Left Ventricular / pathology*
  • Immunohistochemistry
  • Kidney Cortex / innervation
  • Kidney Cortex / metabolism
  • Kidney Cortex / pathology
  • Kidney Medulla / innervation
  • Kidney Medulla / metabolism
  • Kidney Medulla / pathology
  • Kidney Tubules, Distal / innervation
  • Kidney Tubules, Distal / metabolism
  • Kidney Tubules, Distal / pathology
  • Kidney Tubules, Proximal / innervation
  • Kidney Tubules, Proximal / metabolism
  • Kidney Tubules, Proximal / pathology
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Myocardium / metabolism
  • Myocardium / pathology
  • Polycystic Kidney, Autosomal Recessive / complications
  • Polycystic Kidney, Autosomal Recessive / genetics
  • Polycystic Kidney, Autosomal Recessive / pathology*
  • Predictive Value of Tests
  • Rats
  • Rats, Inbred Lew
  • Rats, Mutant Strains*
  • Renin-Angiotensin System / physiology
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / physiology
  • Sympatholytics / pharmacology
  • Time Factors
  • Urea / blood

Substances

  • Antibodies, Monoclonal
  • Biomarkers
  • Sympatholytics
  • Urea
  • Creatinine