This Article Full Text Full Text (PDF) All Versions of this Article: 46/1/58    most recent 01.HYP.0000171587.44736.bav1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yoneda, M. Articles by Felder, R. A. Search for Related Content PubMed PubMed Citation Articles by Yoneda, M. Articles by Felder, R. A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information High Blood Pressure Hazardous Substances DB POTASSIUM Related Collections Other hypertension ACE/Angiotension receptors Hypertension - basic studies

(Hypertension. 2005;46:58.)
© 2005 American Heart Association, Inc.

Original Articles

Differential Effects of Angiotensin II Type-1 Receptor Antisense Oligonucleotides on Renal Function in Spontaneously Hypertensive Rats

Minoru Yoneda; Hironobu Sanada; Junichi Yatabe; Sanae Midorikawa; Shigeatsu Hashimoto; Midori Sasaki; Tetsuo Katoh; Tsuyoshi Watanabe; Peter M. Andrews; Pedro A. Jose; Robin A. Felder

From the Fukushima Medical University School of Medicine (M.Y., H.S., J.Y., S.M., S.H., M.S., T.K., T.W.), Japan; Georgetown University Medical Center (P.M.A., P.A.J.), Washington, DC; and University of Virginia Health Sciences Center (R.A.F.), Charlottesville.

Correspondence to Pedro A. Jose, MD, PhD, Department of Pediatrics, PHC-2, Georgetown University Medical Center, 3800 Reservoir Rd NW, Washington, DC 20007. E-mail pjose01{at}georgetown.edu

The effect of selectively decreasing renal angiotensin II type 1 (AT₁) receptor expression on renal function and blood pressure has not been determined. Therefore, we studied the consequences of selective renal inhibition of AT₁ receptor expression in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) in vivo. Vehicle, AT₁ receptor antisense oligodeoxynucleotides (AS-ODN), or scrambled oligodeoxynucleotides were infused chronically into the cortex of the remaining kidney of conscious, uninephrectomized WKY and SHR on a 4% NaCl intake. Basal renal cortical membrane AT₁ receptor protein was greater in SHR than in WKY. In WKY and SHR, AS-ODN decreased renal but not cardiac AT₁ receptors. AT₁ receptor AS-ODN treatment increased plasma renin activity to a greater extent in WKY than in SHR. However, plasma angiotensin II and aldosterone were increased by AS-ODN to a similar degree in both rat strains. In SHR, sodium excretion was increased and sodium balance was decreased by AS-ODN but had only a transient ameliorating effect on blood pressure. Urinary protein and glomerular sclerosis were markedly reduced by AS-ODN–treated SHR. In WKY, AS-ODN had no effect on sodium excretion, blood pressure, or renal histology but also modestly decreased proteinuria. The major consequence of decreasing renal AT₁ receptor protein in the SHR is a decrease in proteinuria, probably as a result of the amelioration in glomerular pathology but independent of systemic blood pressure and circulating angiotensin II levels.

Key Words: receptors, angiotensin II • rats • kidney • hypertension, essential • proteinuria

This article has been cited by other articles:

				J. C. Sullivan, L. Semprun-Prieto, E. I. Boesen, D. M. Pollock, and J. S. Pollock Sex and sex hormones influence the development of albuminuria and renal macrophage infiltration in spontaneously hypertensive rats Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2007; 293(4): R1573 - R1579. [Abstract] [Full Text] [PDF]

				H. Sanada, J. Yatabe, S. Midorikawa, T. Katoh, S. Hashimoto, T. Watanabe, J. Xu, Y. Luo, X. Wang, C. Zeng, et al. Amelioration of Genetic Hypertension by Suppression of Renal G Protein-Coupled Receptor Kinase Type 4 Expression Hypertension, June 1, 2006; 47(6): 1131 - 1139. [Abstract] [Full Text] [PDF]