Intrarenal localization of angiotensin II type 1 receptor mRNA in the rat

Y Kakinuma, A Fogo, T Inagami, I Ichikawa - Kidney international, 1993 - Elsevier
Y Kakinuma, A Fogo, T Inagami, I Ichikawa
Kidney international, 1993Elsevier
Intrarenal localization of angiotensin II type 1 receptor mRNA in the rat. We examined
intrarenal localization of angiotensin II type 1 receptor (AT1) mRNA in kidneys of normal
adult male Munich Wistar rats using the methods of reverse transcription-polymerase chain
reaction (RT-PCR) and in situ hybridization. For RT-PCR, we used a rat AT1 subtype A
(AT1A)-specific oligonucleotide primer pair. To semiquantitatively assess the expression
level of AT1 mRNA among several regions of kidney, AT1 cDNA was coamplified with β …
Intrarenal localization of angiotensin II type 1 receptor mRNA in the rat. We examined intrarenal localization of angiotensin II type 1 receptor (AT1) mRNA in kidneys of normal adult male Munich Wistar rats using the methods of reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. For RT-PCR, we used a rat AT1 subtype A (AT1A)-specific oligonucleotide primer pair. To semiquantitatively assess the expression level of AT1 mRNA among several regions of kidney, AT1 cDNA was coamplified with β-actin cDNA. When compared to the level in the adrenal gland (expressed as 100%), the level of AT1 mRNA was markedly higher in glomeruli (273 ± 69%), followed in intensity by the renal papilla (151 ± 57%), renal cortex (139 ± 19%), and renal medulla (114 ± 35%). In situ hybridization studies, using a 479 bp nucleotide fragment from AT1A-coding exon as a probe, also revealed a glomerular preponderant pattern of AT1 mRNA localization. Thus, within the glomerulus, AT1 mRNA localized in mesangial areas, predominantly at the vascular pole. In the vascular components of the juxtaglomerular apparatus (JGA), namely the terminal portion of the afferent arteriole (that is, immunohistochemically renin-positive site) and extraglomerular mesangial cells, the latter showed AT1 mRNA localization in the non-manipulated kidney, while AT1 mRNA was undetectable in the arteriole outside the JGA. The kidneys of rats treated with an angiotensin I converting enzyme inhibitor (ACEI) showed extension of the AT1 mRNA localization on the afferent arteriole toward the interlobular artery. We speculate that the observed pattern of AT1 mRNA localizing in the glomerular vascular pole and JGA may account for the unique physiological and pathophysiological actions of angiotensin II (Ang II), that is: (1) the renal hemodynamic effect of Ang II involves simultaneous increases in afferent and efferent arteriolar resistances and a reduction in ultrafiltration coefficient; (2) experimental glomerular sclerosis, sensitive to pharmacological inhibition of angiotensin II, is commonly prominent at the vascular pole; and (3) a negative feedback relationship exists between angiotensin II and renin, presumably via the AT1 on the JGA.
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