Divergent Regulation of Circulating and Intrarenal Renin-Angiotensin Systems in Response to Long-Term Blockade

Vol. 25, No. 4, 2005

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Original Report: Laboratory Investigation

Divergent Regulation of Circulating and Intrarenal Renin-Angiotensin Systems in Response to Long-Term Blockade
Sherry O. Kasper^a, Nidia Basso^c, María Luisa Kurnjek^c, Nora Paglia^c, Carlos M. Ferrario^a, Leon F. Ferder^{b, c}, Debra I. Diz^a

^aHypertension and Vascular Disease Center and Physiology/Pharmacology Department, Wake Forest University School of Medicine, Winston-Salem, N.C.,
^bDepartment of Physiology and Pharmacology, Ponce School of Medicine, Ponce, P.R., USA;
^cLaboratory of Cardiovascular Physiopathology, Department of Pathology, University of Buenos Aires School of Medicine, Buenos Aires, Argentina

Address of Corresponding Author

Am J Nephrol 2005;25:335-341 (DOI: 10.1159/000086571)

Key Words

Angiotensin-converting enzyme inhibitors
Aging
Angiotensin II
Angiotensin receptor blockers
Kidney

Abstract

Background/Aims: Long-term treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin (Ang) II type I (AT₁) receptor blockers can improve kidney function and attenuate the progressive decline in kidney function associated with age. In this study in Wistar rats medicated for 22 months, we determined the effects of enalapril (10 mg/kg/day) and losartan (30 mg/kg/day) treatment, in comparison with vehicle (tap water), on renal AngII receptor density and circulating and urinary components of the renin-angiotensin system (RAS). Methods: Kidney sections were incubated with [¹²⁵I-sarcosine¹-threonine⁸]AngII (0.6 nM) for Ang receptor density, and Ang peptides were determined using radioimmunoassays. Results: Receptor density was ~50% higher in vasa recta, glomeruli, and tubulointerstitium in enalapril-treated rats and lower in vasa recta and glomeruli in losartan-treated relative to vehicle-treated rats. Losartan and enalapril treatment elevated plasma levels of AngI and Ang-(1-7) while AngII increased only in losartan-treated rats. In contrast, both treatments were associated with a reduction in urinary excretion of all three Ang peptides as compared with control rats. Conclusion: The reduction in urinary Ang peptides with losartan and enalapril treatment suggests that blockade of intrarenal AngII may be an important mechanism underlying the renoprotection seen with such treatments.

Author Contacts

Debra I. Diz, PhD
Hypertension and Vascular Disease Center
Wake Forest University School of Medicine, Medical Center Boulevard
Winston-Salem, NC 27157-1032 (USA)
Tel. +1 336 716 2150, Fax +1 336 716 2456, E-Mail ddiz@wfubmc.edu

Article Information

Received: February 22, 2005
Accepted: May 19, 2005
Published online: June 22, 2005
Number of Print Pages : 7
Number of Figures : 3, Number of Tables : 0, Number of References : 40

Medline Abstract (ID 15976496)

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