IngentaConnect DIFFERENTIAL REGULATION OF ANGIOTENSIN II RECEPTORS DURING RENAL ...

Authors: Joly, Emma¹; Nonclercq, Denis²; Caron, Nathalie¹; Mertens, Jeannine³; Flamion, Bruno³; Toubeau, Gerard²; Kramp, Ronald¹; Bouby, Nadine⁴

Source: Clinical and Experimental Pharmacology and Physiology, Volume 32, Number 4, April 2005 , pp. 241-248(8)

Publisher: Blackwell Publishing

Abstract:

SUMMARY

1. The renin-angiotensin system may be involved in the compensatory adaptations occurring after the reduction of renal mass and during the consecutive changes leading to chronic renal failure. We therefore investigated the regulation of angiotensin II receptors in two models of renal hypertrophy in the rat: hypertrophy following uninephrectomy (UNx) or subtotal nephrectomy (STNx). The level of angiotensin type 1 (AT_1A-R and AT_1B-R) and type 2 (AT₂-R) receptor mRNA was quantified by competitive reverse transcription-polymerase chain reaction (RT-PCR) in specific renal zones and the intrarenal distribution of angiotensin II receptors was analysed by immunohistochemistry.

2. In the UNx rats, AT₁-R mRNA expression was not modified in the cortex or in the inner stripe of the outer medulla of the residual kidney at any time after the surgery (1, 4 and 12 weeks). In contrast, AT₁-R mRNA expression was significantly reduced in these zones in STNx rats (-33% and -40%, respectively). This downregulation was organ-specific, as AT₁-R mRNA levels were not modified in the liver. The proportions of AT₁-R subtype (AT_1A and AT_1B) mRNA were unchanged by UNx or STNx. Very low levels of AT₂-R mRNA were found in the cortex of all groups. Immunostaining revealed a similar localization of AT₁-R in mesangial cells, proximal tubule, basolateral membrane of thick ascending limb, in both models of hypertrophy. AT₁-R labelling was also detected in the apical membrane of intercalated cells of cortical collecting ducts.

3. This differential mRNA expression of angiotensin II receptors during compensatory hypertrophy and renal injury suggests that the development of renal hypertrophy is independent of AT₁-R and AT₂-R gene expression levels.

Keywords: angiotensin II; AT1A-R; AT1B-R; AT2-R; chronic renal failure; renal compensatory hypertrophy

Document Type: Research article

DOI: 10.1111/j.1440-1681.2005.04181.x

Affiliations: 1: Laboratory of Physiology and Pharmacology, 2: Laboratory of Histology, Faculty of Medicine and Pharmacy, University of Mons-Hainaut, Mons, Belgium, 3: Molecular Physiolology Research Unit, University of Namur, Namur, Belgium, and 4: INSERM U652, Paris, France

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DIFFERENTIAL REGULATION OF ANGIOTENSIN II RECEPTORS DURING RENAL INJURY AND COMPENSATORY HYPERTROPHY IN THE RAT