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

Journal Article


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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 ± 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.

Authors


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

Publication Date


  • 2007

Citation


  • Phillips, J. K., Hopwood, D., Loxley, R. A., Ghatora, K., Coombes, J. D., Tan, Y., Harrison, J. L., McKitrick, D. J., Holobotvskyy, V., Arnolda, L. F. & Rangan, G. K. (2007). Temporal relationship between renal cyst development, hypertension and cardiac hypertrophy in a new rat model of autosomal recessive polycystic kidney disease. Kidney and Blood Pressure Research, 30 (3), 129-144.

Scopus Eid


  • 2-s2.0-34250875018

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1832&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/809

Has Global Citation Frequency


Number Of Pages


  • 15

Start Page


  • 129

End Page


  • 144

Volume


  • 30

Issue


  • 3

Place Of Publication


  • Switzerland

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.

Authors


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

Publication Date


  • 2007

Citation


  • Phillips, J. K., Hopwood, D., Loxley, R. A., Ghatora, K., Coombes, J. D., Tan, Y., Harrison, J. L., McKitrick, D. J., Holobotvskyy, V., Arnolda, L. F. & Rangan, G. K. (2007). Temporal relationship between renal cyst development, hypertension and cardiac hypertrophy in a new rat model of autosomal recessive polycystic kidney disease. Kidney and Blood Pressure Research, 30 (3), 129-144.

Scopus Eid


  • 2-s2.0-34250875018

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1832&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/809

Has Global Citation Frequency


Number Of Pages


  • 15

Start Page


  • 129

End Page


  • 144

Volume


  • 30

Issue


  • 3

Place Of Publication


  • Switzerland