Accelerated fibrosis and collagen deposition develop in the renal interstilium of angiotensin type 2 receptor null mutant mice during ureteral obstruction. We examined the role of angiotensin in renal remodeling that is specifically channeled through the angiotensin type 2 receptor (2 receptor). Previously, we observed that in mouse embryonic kidneys the AT1 mRNA is predominantly expressed in the mesenchynle. We therefore chose a model of unilateral ureteral obstrtryction, character-ized by activation of the renin-angiotensin system, while fibrosis develops prominently within the renal interstitium. Male wild-type mice (Ago-2/Y) and mice null mutanl for the AT2 gene (Agtr2-/N) were subujected to a complete unilateral ureteral ligation for 5 or 14 days. Obstructed idneys of Agtr2-/Y mice showed more severe interstitial fibrosis than Ihose of Agtr2-/Y mice. confirmed by increased collagen hy point-counting on Masson trichrome stained sections, and increased oH (I) collagen mRNA expression by Northern blot. Lmmunohistoehernistry staining for PCNA (a marker of cell proliferation), 14: 80 (a marker of acmphages), vimendn (a marker of flbroblasls), and aSMA (a marker of myofibroblasts) revealed that, while the two groups were comparable in the degree of cell proliferation and macrophagc infiltration, fibroblasts/myofibrofilasts were present in a greater abundance in obslructed kidneys of Agtr2-/Y mice than in Agtr2+/Y al both 5 and 14 days after obstruction. Moreuver. cclls undergoing apopiosis were significantly tess in Agtr2-/Y tilth in Agtr2+/Y. Thus, the AT: receptor significantly impacls the remodeling process within renal inlcrstitium, potentially by reguhuing the population) of colblgen-producing cells. While inost of the known effects of angiotensin 11 (Aug 11) are mediated by its type 1 receplor (AT1 [1], the function of type 2 receptor (AT2) has not been fully elucidated. Some investigators suggest that AT2, is involved in control of cell prolileration and differentiation [2. 3] Several recent studies indicate thai AT,. Is involved in apoplosis [4. 5]. Although AT, expression is down- regulated after birth, il is speculated that AT2 plays a role in tissue remodeling or repair of vascular and cutaneous tissues under some pathophysiological conditions [6-9]. It has been widely accepted that, in a variety of renal diseases,