| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Pediatrics and Pediatric Rearch Institute, Saint Louis University, St. Louis, MO, USA
* To whom correspondence should be addressed. E-mail: mloghman{at}att.net.
Hypertension is a common complication of autosomal dominant polycystic kidney disease (ADPKD1), often present before the onset of renal failure. A role for the renin-angiotensin system (RAS) has been proposed but studies of systemic RAS have failed to show a correlation between plasma renin activity and blood pressure in ADPKD. Ectopic renin expression by cyst epithelium was first reported by Torres et al. in 1992. It is not known, however, if other RAS components are also expressed by cysts in ADPKD. We show that, in addition to renin, angiotensinogen (AGT) is produced by some cysts and dilated tubules. Angiotensin converting enzyme, angiotensin II type 1 receptor (AT1), and angiotensin II (Ang II) peptide are also present within cysts and in many tubules; and some cyst fluids contain high Ang II concentrations. Additionally, cyst-derived cells in culture continue to express the components of the RAS both at protein and mRNA level. We further show that renin is expressed primarily in cysts of distal tubule origin and in cyst-derived cells with distal tubule characteristics, while AGT is expressed primarily in cysts of proximal tubule origin and in cyst-derived cells with proximal tubule characteristics. Renin production by cyst-derived cells appears to be regulated by extracellular Na+ concentration. Based on these observations, we propose a model of an autocrine/paracrine RAS in polycystic kidney disease, whereby overactivity of the intrarenal system results in sustained increases in intratubular Ang II concentrations.
This article has been cited by other articles:
|
|
 |
|
  R. W. Schrier Renal Volume, Renin-Angiotensin-Aldosterone System, Hypertension, and Left Ventricular Hypertrophy in Patients with Autosomal Dominant Polycystic Kidney Disease J. Am. Soc. Nephrol., September 1, 2009; 20(9): 1888 - 1893. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Cadnapaphornchai, K. McFann, J. D. Strain, A. Masoumi, and R. W. Schrier Prospective Change in Renal Volume and Function in Children with ADPKD Clin. J. Am. Soc. Nephrol., April 1, 2009; 4(4): 820 - 829. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Park, W. E. Sweeney, G. Jia, R. J. Roman, and E. D. Avner 20-HETE Mediates Proliferation of Renal Epithelial Cells in Polycystic Kidney Disease J. Am. Soc. Nephrol., October 1, 2008; 19(10): 1929 - 1939. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. H. Gattone II, T. M. Siqueira Jr, C. R. Powell, C. M. Trambaugh, J. E. Lingeman, and A. L. Shalhav Contribution of Renal Innervation to Hypertension in Rat Autosomal Dominant Polycystic Kidney Disease Experimental Biology and Medicine, August 1, 2008; 233(8): 952 - 957. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Zafar, Y. Tao, S. Falk, K. McFann, R. W. Schrier, and C. L. Edelstein Effect of statin and angiotensin-converting enzyme inhibition on structural and hemodynamic alterations in autosomal dominant polycystic kidney disease model Am J Physiol Renal Physiol, September 1, 2007; 293(3): F854 - F859. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R Lawson, T. W Doulton, and G. A MacGregor Review: Autosomal Dominant Polycystic Kidney Disease: Role of the Renin-Angiotensin System in Raised Blood Pressure in Progression of Renal and Cardiovascular Disease Journal of Renin-Angiotensin-Aldosterone System, September 1, 2006; 7(3): 139 - 145. [Abstract] [PDF]
|
|
|
|
|
|
H. Haller, J.-K. Park, C. Lindschau, M. Meyer, and J. Menne Intrarenal renin-angiotensin system -- important player of the local milieu Journal of Renin-Angiotensin-Aldosterone System, June 1, 2006; 7(2): 122 - 125. [PDF]
|
|
|
|
 |
|
 B. T. Alexander Fetal programming of hypertension Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2006; 290(1): R1 - R10. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Loghman-Adham, C. E. Soto, T. Inagami, and C. Sotelo-Avila Expression of Components of the Renin-angiotensin System in Autosomal Recessive Polycystic Kidney Disease J. Histochem. Cytochem., August 1, 2005; 53(8): 979 - 988. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Shimizu, T. Oishi, A. Omori, A. Sugiura, K. Hirota, H. Aoyama, T. Saito, T. Sugaya, Y. Kon, J. D. Engel, et al. Identification of cis-Regulatory Sequences in the Human Angiotensinogen Gene by Transgene Coplacement and Site-Specific Recombination Mol. Cell. Biol., April 15, 2005; 25(8): 2938 - 2945. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Paterson, R. Magistroni, N. He, K. Wang, A. Johnson, P. R. Fain, E. Dicks, P. Parfrey, P. St. George-Hyslop, and Y. Pei Progressive Loss of Renal Function Is an Age-Dependent Heritable Trait in Type 1 Autosomal Dominant Polycystic Kidney Disease J. Am. Soc. Nephrol., March 1, 2005; 16(3): 755 - 762. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
