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(Hypertension. 1995;25:872-877.)
© 1995 American Heart Association, Inc.

Articles

Differential Regulation of Angiotensin II Receptor Subtypes in Rat Kidney by Low Dietary Sodium

Yong Du; Aqing Yao; Dengfu Guo; Tadashi Inagami; Donna H. Wang

From the Department of Internal Medicine, Hypertension and Vascular Research, University of Texas Medical Branch, Galveston (Y.D., A.Y., D.H.W.), and the Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tenn (D.G., T.I.).

Correspondence to Donna H. Wang, MD, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555-1065.

Abstract This study was designed to determine whether expression of renal messenger RNA (mRNA) encoding the two known angiotensin II type 1 (AT₁ ) receptor subtypes (AT_1A and AT_1B) can be regulated by dietary sodium. Seven-week-old male Wistar rats were fed a low-sodium diet (0.07%, n=9) or a normal-sodium diet (0.5%, n=9 [control]) for 14 days. A rat AT₁ complementary DNA (cDNA) probe, which hybridizes to mRNA encoding both the AT_1A and AT_1B receptor subtypes, and cDNA probes, which are selective for AT_1A or AT_1B mRNA, were used in Northern blot or in situ hybridization analysis. By use of Northern blot analysis, renal mRNA levels for the AT₁ and AT_1A receptors in rats fed a low-sodium diet were found to be increased twofold (P<.05) compared with control. Because renal AT_1B mRNA content was not detected by Northern blot analysis, quantitative image analysis of in situ hybridization with a digoxigenin-labeled cRNA probe made from AT_1B cDNA was used. In situ hybridization analysis indicated that AT_1B mRNA was expressed in the proximal and collecting tubules of the kidney in rats fed a normal-sodium diet. The low-sodium diet significantly decreased the percent positive staining area of AT_1B mRNA in the renal cortex (5.51±0.77% versus 2.73±0.35%, P<.05) and medulla (4.76±0.70% versus 2.01±0.43%, P<.05) compared with the control diet. These results indicate that the increase in AT₁ mRNA levels in the kidney induced by low sodium intake is the result of a selective increase in AT_1A mRNA and suggest that AT_1A is the predominant receptor subtype of AT₁ in the kidney. The data also suggest that dietary sodium differentially modulates the expression of genes encoding AT₁ receptor subtypes, because there is an inverse relationship between the expression of the AT_1A and AT_1B subtypes in response to a low-sodium diet. The functional implications are discussed.

Key Words: receptors, angiotensin • sodium, dietary • gene expression regulation • blotting, Northern • in situ hybridization

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