HIV-associated nephropathy: role of AT2R

Abstract

AT(1)R has been reported to play an important role in the progression of HIV-associated nephropathy (HIVAN); however, the effect of AT(2)R has not been studied. Age and sex matched control (FVB/N) and Tg26 mice aged 4, 8, and 16weeks were studied for renal tissue expression of AT(1)R and AT(2)R (Protocol A). Renal tissue mRNA expression of AT(2)R was lower in Tg26 mice when compared with control mice. In Protocol B, Tg26 mice were treated with either saline, telmisartan (TEL, AT(1) blocker), PD123319 (PD, AT(2)R blocker), or TEL+PD for two weeks. TEL-receiving Tg26 (TRTg) displayed less advanced glomerular and tubular lesions when compared with saline-receiving Tg26 (SRTg). TRTgs displayed enhanced renal tissue AT(2)R expression when compared to SRTgs. Diminution of renal tissue AT(2)R expression was associated with advanced renal lesions in SRTgs; whereas, upregulation of AT(2)R expression in TRTgs was associated with attenuated renal lesions. PD-receiving Tg26 mice (PDRTg) did not show any alteration in the course of HIVAN; whereas, PD+TEL-receiving Tg26 (PD-TRTg) showed worsening of renal lesions when compared to TRTgs. Interestingly, plasma as well as renal tissues of Tg26 mice displayed several fold higher concentration of Ang III, a ligand of AT(2)R.