PPARs in the Renal Regulation of Systemic Blood Pressure

Figure 3

Paracrine effects of the RAAS and their modulation by PPAR$\gamma$. In adipocytes (a) PPAR$\gamma$ activation is suggested to reduce ATG synthesis, impeding RAAS activation; this can ameliorate hypertension in obese diabetic patients. Independently of RAAS modulation, PPAR$\gamma$ improves insulin action in adipocytes, reducing the production of proinflammatory cytokines and reducing the risk of atherogenesis and nephropathy. In kidney mesangial cells (b) PPAR$\gamma$ activation reduces TGF$\beta$-mediated hypertrophy and downregulates expression of AT-R1 and ACE. Some PPAR$\gamma$ ligands, such as telmisartan, combine AT-R1 blocking and ACE inhibitor properties, effectively inhibiting the proinflammatory actions of Ang-II in the kidney. This dual action can also reduce vascular inflammation resulting from VSMC dysfunction (c) and cardiomyocyte hyprtreophy in chronic hypertension (d). We labeled with asterisks PPAR$\gamma$, where its ligands can act through both direct AT-R1 inhibition and downregulation of ACE/AT-R1 gene expression. TGF$\beta$: transforming growth factor-$\beta$, ECM: extracellular matrix, VCAM: vascular cell adhesion molecule, ROS: reactive oxygen species, $\alpha$MHC/$\beta$MHC: myosin heavy chain $\alpha$/$\beta$, ANF: atrial natriuretic factor.