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

J.K. Phillips, D. Hopwood, R.A. Loxley, K. Ghatora, J.D. Coombes, Y.S. Tan, J.L. Harrison, Doug Mckitrick, Vasyl Holobotovskyy, Leonard Arnolda

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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 8 6 mu mol/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 mu m, 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 <= .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. Copyright (c) 2007 S. Karger AG, Basel.
Original languageEnglish
Pages (from-to)129-144
JournalKidney and Blood Pressure Research
Volume30
Issue number3
DOIs
Publication statusPublished - 2007

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