[Peroxisome proliferator-activated receptor activator troglitazone inhibits angiotensin II-stimulated secretion of vasoactive factors by endothelial cells].
OBJECTIVE
To investigate the effects of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligand on angiotensin II (AngII)-induced endothelin-1 (ET-1) and NO secretion by endothelial cells in comparison with AngII type I receptor (AT1R) antagonist losartan, so as to reveal the relationship between PPAR gamma and essential hypertension.


METHODS
Cultured human umbilical vein endothelial cells (HUVECs) were treated with AngII, PPAR gamma ligand troglitazone, AngII plus troglitazone, and AngII plus AT1R antagonist losartan, respectively, and the concentrations of NO and ET-1 in the cell culture supernatant were measured to evaluate the effects of troglitazone and losartan on AngII-induced NO and ET-1 production by human endothelial cells.


RESULTS
Treatment of the HUVECs with troglitazone at 10 micromol/L and 50 micromol/L did not produce significant changes in ET-1 concentration in the cell culture supernatants, but significantly increased NO concentration as compared with the control group (P<0.05). Triglitazone at the concentration of 50 micromol/L significantly inhibited AngII (1x10(-6) mol/L)-induced ET-1 production (P<0.05), and at both 10 and 50 micromol/L, troglitazone inhibited the NO release-lowering effect of AngII in the endothelial cells (P<0.05). Both troglitazone and losartan inhibited AngII-induced ET-1 production by the endothelial cells, but losartan showed more potent effect (P<0.05). Similarly, both troglitazone and losartan inhibited decreased NO production in response to AngII treatment, and again losartan showed stronger effect (P<0.05).


CONCLUSIONS
PPAR gamma ligand troglitazone can inhibit AngII-induced ET-1 production enhancement and decreased NO release by the endothelial cells, but its effect is not so strong as losartan, suggesting that troglitazone modulates blood pressure not solely through AT1R pathway.
Li
Yong-qin
YQ
Department of Cardiology, Second Hospital of Xi'an Jiaotong University, and Department of Pathophysiology, Xi'an Jiaotong University, China.
Niu
Xiao-lin
XL
Wang
Cong-xia
CX
Wei
Jing
J
Wang
Shi-jie
SJ
Zhou
Juan
J
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002460:Cell Line; D002839:Chromans / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D019332:Endothelin-1 / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000378:metabolism; D007150:Immunohistochemistry; D019808:Losartan / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D002839:Chromans; D019332:Endothelin-1; D047495:PPAR gamma; D044140:Receptor, Angiotensin, Type 1; D045162:Thiazolidinediones; D000804:Angiotensin II; D009569:Nitric Oxide; D000077288:Troglitazone; D019808:Losartan