PPAR-gamma activation inhibits angiotensin II synthesis, apoptosis, and proliferation of mesangial cells from spontaneously hypertensive rats.

The angiotensin II level is elevated in subjects genetically prone to develop hypertension, triggering renal hypercellularity, cytokine production, and matrix deposition. Angiotensin-converting enzyme inhibition and/or angiotensin II type 1 receptor blockade attenuate renal damage. Rosiglitazone, a peroxisome proliferator-activated receptor gamma agonist possessing antihypertensive and anti-inflammatory properties, was demonstrated to provide better renal protection than angiotensin-converting enzyme inhibitors. We studied the effects of in vivo peroxisome proliferator-activated receptor gamma activation by rosiglitazone on angiotensin II synthesis, proliferation, and apoptosis of mesangial cells of spontaneously hypertensive rats versus normotensive Sprague-Dawley rats. The animals consumed either a high-sodium diet (8% Na) or a normal-sodium diet (0.5% Na). Half of each group received rosiglitazone at 5 mg/kg/day. After 3 weeks, all rats were sacrificed and the mesangial cells isolated and cultured. Angiotensin II was assessed by radioimmunoassay, apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, and cell proliferation by [(3)H]thymidine incorporation. Only the spontaneously hypertensive rats which consumed the high-sodium diet developed hypertension (185 +/- 6 mm Hg vs. basal 128 +/- 5 mm Hg; p = 0.0007) which was attenuated by rosiglitazone (to 126 +/- 4 mm Hg; p = 0.34). Angiotensin II synthesis, proliferation, and apoptosis were exaggerated in mesangial cell cultures from Sprague-Dawley rats and, more so, spontaneously hypertensive rats fed the high-sodium diet, but were inhibited in cultures from rosiglitazone-treated animals. Peroxisome proliferator-activated receptor gamma activation, in addition to lowering blood pressure, suppresses angiotensin II synthesis and downregulates angiotensin-II-mediated proliferation and apoptosis of mesangial cells. In the context of hypertension-induced renal damage, this would mean that the renoprotective role of rosiglitazone extends beyond glycemic and lipidemic control.

Efrati S ，Berman S ，Ilgiyeav E ，Averbukh Z ，Weissgarten J ... -  《nephron experimental nephrology》

Apoptosis and proliferation of cultured mesangial cells isolated from kidneys of rosiglitazone-treated pregnant diabetic rats.

Weissgarten J ，Berman S ，Efrati S ，Rapoport M ，Averbukh Z ，Feldman L ... -  《NEPHROLOGY DIALYSIS TRANSPLANTATION》

Vasculoprotective effects of rosiglitazone through modulating renin-angiotensin system in vivo and vitro.

Ren L ，Liu N ，Zhi H ，Li Y ，Li Y ，Tang R ，Sheng Z ... -  《-》

Enhanced angiotensin II production by renal mesangium is responsible for apoptosis/proliferation of endothelial and epithelial cells in a model of malignant hypertension.

Efrati S ，Berman S ，Goldfinger N ，Erez N ，Averbukh Z ，Golik A ，Rotter V ，Weissgarten J ... -  《-》

PPAR gamma agonists partially restores hyperglycemia induced aggravation of vascular dysfunction to angiotensin II in thoracic aorta isolated from rats with insulin resistance.

Gaikwad AB ，Viswanad B ，Ramarao P 《PHARMACOLOGICAL RESEARCH》