Type 1A angiotensin II receptor is regulated differently in proximal and distal nephron segments

Angiotensin II plays important roles in renal vasoconstriction, sodium reabsorption in proximal tubules, and cell proliferation. Angiotensin II receptors are present not only in proximal but also in distal tubules. We investigated the effects of dehydration on the mRNA expression of type 1A angiotensin II receptor (AT1A) in proximal and distal nephron segments and on the expression of type 1 angiotensin II receptor (AT1) protein. Competitive polymerase chain reaction was employed to quantitatively examine mRNA expression, and AT1-specific polyclonal antibody was used for Western blot analysis. AT1A mRNA expression was most abundant in glomeruli. Collecting ducts showed higher expressions than did proximal tubules or thick ascending limbs. Dehydration caused an increase of AT1A mRNA expression in glomeruli, proximal straight tubules (PST), and medullary and cortical thick ascending limbs (MAL and CAL, respectively). In contrast, dehydration decreased AT1A mRNA expression in cortical, outer medullary, and inner medullary collecting ducts (CCD, OMCD, and IMCD, respectively). Incubation of isolated glomeruli, PST, and IMCD in hypertonic solution made by NaCl and mannitol in vitro increased AT1A mRNA expression. Incubation of IMCD with AVP (10(-7) mol/l) also increased AT1A mRNA expression. AT1 was detected at 45 kDa by Western blotting. Dehydration caused a decrease and increase of AT1 expression in the cortex and the medulla, respectively. In summary, these data showed that the mechanisms of the regulation of AT1A differ between proximal and distal tubules. The finding that AT1 was up-regulated in the medulla during dehydration may suggest that this receptor plays an important role in dehydration in the distal tubules.