Differential regulation of angiotensin II receptor subtypes in rat kidney by low dietary sodium

Y Du, A Yao, D Guo, T Inagami, DH Wang - Hypertension, 1995 - Am Heart Assoc
Y Du, A Yao, D Guo, T Inagami, DH Wang
Hypertension, 1995Am Heart Assoc
This study was designed to determine whether expression of renal messenger RNA (mRNA)
encoding the two known angiotensin II type 1 (AT1) receptor subtypes (AT1A and AT1B) 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 AT1A and
AT1B receptor subtypes, and cDNA probes, which are selective for AT1A or AT1B mRNA …
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 (AT1A and AT1B) 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 AT1A and AT1B receptor subtypes, and cDNA probes, which are selective for AT1A or AT1B mRNA, were used in Northern blot or in situ hybridization analysis. By use of Northern blot analysis, renal mRNA levels for the AT1 and AT1A receptors in rats fed a low-sodium diet were found to be increased twofold (P<.05) compared with control. Because renal AT1B mRNA content was not detected by Northern blot analysis, quantitative image analysis of in situ hybridization with a digoxigenin-labeled cRNA probe made from AT1B cDNA was used. In situ hybridization analysis indicated that AT1B 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 AT1B 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 AT1A mRNA and suggest that AT1A 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 AT1A and AT1B subtypes in response to a low-sodium diet. The functional implications are discussed.
Am Heart Assoc