Angiotensin type 2 receptor is expressed in the adult rat kidney and promotes cellular proliferation and apoptosis.
BACKGROUND
Angiotensin II (Ang II) is associated with cell proliferation and apoptosis. The role of the angiotensin type 2 receptor (AT2R) in these processes remains controversial. Conventional radioligand binding of 125I-Sar1, Ile8 Ang II in adult kidney has failed to demonstrate the binding for the AT2R.


METHODS
The presence of the AT2R was explored in adult rat kidney by in vitro and in vivo autoradiography using the selective AT2R radioligand 125I-CGP 42112B. The roles of the angiotensin type 1 receptor (AT1R) and the AT2R in mediating cellular proliferation and apoptosis were assessed using selective AT1R or AT2R antagonists in Ang II-infused Sprague-Dawley (SD) rats.


RESULTS
125I-CGP 42112B binding was demonstrated by in vitro and in vivo autoradiography techniques in the glomeruli and proximal tubules of SD rats. This binding could be displaced by Ang II and the AT2R antagonist PD123319 but not by the AT1R antagonist valsartan. Subcutaneous infusion of Ang II for 14 days in eight-week-old SD rats induced proliferation of proximal tubular epithelial cells, as assessed by a twofold increase in proliferating cell nuclear antigen (PCNA)-positive cells and apoptosis, as assessed by a threefold increase in terminal dUTP nick end labeling (TUNEL)-positive cells. The administration of the AT2R antagonist PD123319 or the AT1R antagonist valsartan was associated with attenuation of the increases in both PCNA- and TUNEL-positive cells following Ang II infusion. Ang II infusion was associated with increased osteopontin gene and protein expression, which could be reduced by treatment with either valsartan or PD123319.


CONCLUSIONS
These findings indicate that there is significant expression of the AT2R in the adult kidney, and that the AT2R has a role in mediating Ang II-induced proliferation and apoptosis in proximal tubular epithelial cells and expression of osteopontin.
Cao
Z
Z
Department of Medicine, University of Melbourne, Austin and Repatriation Medical Center (Repatriation Campus),Heidelberg West, Victoria, Australia.
Kelly
D J
DJ
Cox
A
A
Casley
D
D
Forbes
J M
JM
Martinello
P
P
Dean
R
R
Gilbert
R E
RE
Cooper
M E
ME
D000367:Age Factors; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D001345:Autoradiography; D001794:Blood Pressure; D002455:Cell Division / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D007457:Iodine Radioisotopes; D007668:Kidney / Q000737:chemistry / Q000166:cytology* / Q000502:physiology*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D009929:Organ Size; D053495:Osteopontin; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D012795:Sialoglycoproteins / Q000032:analysis / Q000235:genetics; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D000959:Antihypertensive Agents; D007093:Imidazoles; D007457:Iodine Radioisotopes; D009842:Oligopeptides; D018809:Proliferating Cell Nuclear Antigen; D011725:Pyridines; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D013777:Tetrazoles; D053495:Osteopontin; D000804:Angiotensin II; C060894:CGP 42112A; C073402:PD 123319; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C074793:angiotensin II, Sar(1)-; D000068756:Valsartan; D014633:Valine