Thiazolidinediones Suppress Endothelin-1 Secretion from Bovine Vascular Endothelial Cells: A New Possible Role of PPARγ on Vascular Endothelial Function

Satoh, Hiroaki; Tsukamoto, Kazuhisa; Hashimoto, Yoshiaki; Hashimoto, Naoaki; Togo, Masami; Hara, Mariko; Maekawa, Hisato; Iso-O, Naoyuki; Kimura, Satoshi; Watanabe, Tsuyoshi

doi:10.1006/bbrc.1998.0126

Cited by 178 publications

(98 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…20 As suggested by earlier in vitro studies, PPARa and PPARg are potent inhibitors of ET-1 production in vascular cells. 15 This study showed that ET-1 mRNA expression was increased in the kidneys in association with increased blood pressure and decreased GFR. These findings suggest that the enhanced renal production of ET-1 has a role in the development of hypertension and renal dysfunction.…”

Section: Discussionmentioning

confidence: 78%

“…14 Moreover, it provided far better renal protection compared with suppression of the renin-angiotensin system by ACE inhibitors, and is able to suppress ET-1 secretion from endothelial and vascular smooth muscle cells. 15 These findings suggest the ability of protective effects of PPARg activators against hypertensive renal injury. In the kidney, PPARg protein is widely expressed along the nephron segment, 16 but its role in hypertensive renal injury has not yet been determined.…”

Section: Introductionmentioning

confidence: 87%

See 1 more Smart Citation

Rosiglitazone prevents the progression of renal injury in DOCA-salt hypertensive rats

et al. 2010

View full text Add to dashboard Cite

This study was designed to evaluate the possible renoprotective effects of rosiglitazone (RGT), a peroxisome proliferatoractivated subtype c receptor agonist, in deoxycorticosterone acetate (DOCA)-salt hypertension and its role in endogenous endothelin-1 (ET-1) production and renal fibrosis associated with inflammation. Rats were implanted with DOCA strips (200 mg kg À1 ) at 1 week after unilateral nephrectomy. DOCA-salt rats received control diet with or without RGT (10 mg kg À1 per day). Systolic blood pressure was measured by the tail-cuff method. Glomerulosclerosis and tubulointerstitial fibrosis were evaluated on kidney sections. The expression of ED-1, cyclooxygenase-2 (COX-2), heat shock protein-25 (HSP25) and transforming growth factor-b1 (TGF-b1) was determined in the kidney by semiquantitative immunoblotting. In DOCA-salt rats, systolic blood pressure was increased, whereas creatinine clearance decreased compared with controls, which were counteracted by RGT treatment. Tubular injury and glomerulosclerois in the histological study were prominent in DOCA-salt rats, which were counteracted by RGT treatment. ET-1 expression was increased in DOCA-salts rats, which was attenuated by RGT treatment. The expression of TGF-b1, ED-1 and COX-2 was increased in DOCA-salt, which was attenuated by RGT treatment. In conclusion, RGT treatment decreases blood pressure and is effective in preventing the progression of renal injury in DOCA-salt hypertension, the mechanisms of which are associated with anti-inflammatory and anti-fibrotic effects through reducing the overexpression of ET-1, ED-1, COX-2 and TGF-b1 in the kidney.

show abstract

Section: Discussionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 87%

Rosiglitazone prevents the progression of renal injury in DOCA-salt hypertensive rats

et al. 2010

View full text Add to dashboard Cite

show abstract

“…However, these observations are not supported by the finding that PPAR␥ mRNA is not detected in proximal tubules (18). PPAR␥ is expressed in the vascular system (33), such as in endothelial cells (34,35), vascular smooth muscle cells (36), and monocyte͞macrophages (37,38), where TZDs may affect vascular function, leading to edema. In line with this notion, PPAR␥ activators RGZ and pioglitazone prevent hypertension as well as the vascular changes induced by angiotensin II infusion (39).…”

Section: Discussionmentioning

confidence: 98%

Collecting duct-specific deletion of peroxisome proliferator-activated receptor γ blocks thiazolidinedione-induced fluid retention

Zhang

Kohan

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

315

269

View full text Add to dashboard Cite

The peroxisome proliferator-activated receptor subtype ␥ (PPAR␥) ligands, namely the synthetic insulin-sensitizing thiazolidinedione (TZD) compounds, have demonstrated great potential in the treatment of type II diabetes. However, their clinical applicability is limited by a common and serious side effect of edema. To address the mechanism of TZD-induced edema, we generated mice with collecting duct (CD)-specific disruption of the PPAR␥ gene. We found that mice with CD knockout of this receptor were resistant to the rosiglitazone-(RGZ) induced increases in body weight and plasma volume expansion found in control mice expressing PPAR␥ in the CD. RGZ reduced urinary sodium excretion in control and not in conditional knockout mice. Furthermore, RGZ stimulated sodium transport in primary cultures of CD cells expressing PPAR␥ and not in cells lacking this receptor. These findings demonstrate a PPAR␥-dependent pathway in regulation of sodium transport in the CD that underlies TZD-induced fluid retention.roziglitazone ͉ Cre recombinase ͉ Evans blue technique T hiazolidinediones (TZDs), synthetic insulin-sensitizing drugs that include troglitazone, pioglitazone, and rosiglitazone (RGZ), are highly effective in the treatment of type II diabetes. TZDs are believed to mediate their antidiabetic effect via activation of peroxisome proliferator-activated receptor ␥ (PPAR␥) (1). In addition to lowering blood glucose, these drugs also benefit cardiovascular parameters, such as blood pressure and endothelial function (2, 3). However, fluid retention, presented as rapid weight gain, and peripheral and pulmonary edema have emerged as the most common and serious side effects of TZDs (4-6). Global awareness of this side effect has increased as a result of the growing number of reported cases. In a recent issue of Circulation (7), the American Heart Association and American Diabetes Association jointly issued a Consensus Statement commenting on the safety of TZD as related to edema. The mechanisms of fluid retention in patients treated with TZDs are poorly understood and may involve a number of factors, including reduction of urinary sodium excretion (8), alteration of endothelial permeability (9), increased sympathetic nervous system activity (10), or altered interstitial ion transport (11). To evaluate the relative contributions of these individual mechanisms, tissue-or cell-type-specific approaches are needed in carefully designed studies.PPARs are a group of zinc finger-containing transcription factors, representing a family of the nuclear hormone receptor gene superfamily. To date, three subtypes of PPARs encoded by different genes have been described from several species: PPAR␣, -␤͞␦, and -␥ (12, 13). They share a high degree of similarity in their overall amino acid sequences, particularly in the DNA-binding domain (14). The three isoforms of the PPARs heterodimerize with retinoid X receptor, bind to the same peroxisome proliferatorresponsive element in the promoter regions of their target genes, and modulate gene transcripti...

show abstract

“…Bovine aortic endothelial cells (BAEC) were isolated and cultured as described previously (26) in DMEM supplemented with 10% fetal calf serum (FCS), 100 U/ml penicillin, and 100 µg/ml streptomycin. BAEC between the 5th and 8th passage were used for this study.…”

Section: Cell Culturementioning

confidence: 99%

“…Total RNA was extracted from BAEC cultures at specified times by the acid guanidium thiocyanate phenol chloroform extraction method (26). Northern blotting was performed as described previously (26) using a 1.9 kb EcoR I fragment of bovine prepro-endothelin-1 (b-PpET-1) cDNA (donated by T. Quertermous, Stanford University, Stanford, USA).…”

Section: Rna Isolation and Hybridizationmentioning

confidence: 99%

Endothelin-1 Gene Expression in Endothelial Cells Is Potently Inhibited by a Vasodilator, Dilazep

et al. 2004

View full text Add to dashboard Cite

show abstract

Thiazolidinediones Suppress Endothelin-1 Secretion from Bovine Vascular Endothelial Cells: A New Possible Role of PPARγ on Vascular Endothelial Function

Cited by 178 publications

References 37 publications

Rosiglitazone prevents the progression of renal injury in DOCA-salt hypertensive rats

Rosiglitazone prevents the progression of renal injury in DOCA-salt hypertensive rats

Collecting duct-specific deletion of peroxisome proliferator-activated receptor γ blocks thiazolidinedione-induced fluid retention

Endothelin-1 Gene Expression in Endothelial Cells Is Potently Inhibited by a Vasodilator, Dilazep

Contact Info

Product

Resources

About