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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.
Kidney Blood Press Res. 2007; 30(3):129-44.KB

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.

Authors+Show Affiliations

Division of Health Sciences, School of Veterinary and Biomedical Science, Murdoch University, Perth, Australia. j.k.phillips@murdoch.edu.auNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17446713

Citation

Phillips, Jacqueline K., et al. "Temporal Relationship Between Renal Cyst Development, Hypertension and Cardiac Hypertrophy in a New Rat Model of Autosomal Recessive Polycystic Kidney Disease." Kidney & Blood Pressure Research, vol. 30, no. 3, 2007, pp. 129-44.
Phillips JK, Hopwood D, Loxley RA, et al. 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.
Phillips, J. K., Hopwood, D., Loxley, R. A., Ghatora, K., Coombes, J. D., Tan, Y. S., 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 & Blood Pressure Research, 30(3), 129-44.
Phillips JK, et al. 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. PubMed PMID: 17446713.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Temporal relationship between renal cyst development, hypertension and cardiac hypertrophy in a new rat model of autosomal recessive polycystic kidney disease. AU - Phillips,Jacqueline K, AU - Hopwood,Deborah, AU - Loxley,Rhonda A, AU - Ghatora,Kamaljit, AU - Coombes,Jason D, AU - Tan,Ying Sin, AU - Harrison,Joanne L, AU - McKitrick,Douglas J, AU - Holobotvskyy,Vasyl, AU - Arnolda,Leonard F, AU - Rangan,Gopala K, Y1 - 2007/04/19/ PY - 2006/10/27/received PY - 2007/02/06/accepted PY - 2007/4/21/pubmed PY - 2007/7/18/medline PY - 2007/4/21/entrez SP - 129 EP - 44 JF - Kidney & blood pressure research JO - Kidney Blood Press. Res. VL - 30 IS - 3 N2 - 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. SN - 1423-0143 UR - https://www.unboundmedicine.com/medline/citation/17446713/Temporal_relationship_between_renal_cyst_development_hypertension_and_cardiac_hypertrophy_in_a_new_rat_model_of_autosomal_recessive_polycystic_kidney_disease_ L2 - https://www.karger.com?DOI=10.1159/000101828 DB - PRIME DP - Unbound Medicine ER -