A role for endogenous endothelin-1 in neointimal formation after rat carotid artery balloon angioplasty. Protective effects of the novel nonpeptide endothelin receptor antagonist SB 209670.

Douglas, S A; Louden, Calvert; Vickery-Clark, Lynne M.; Storer, Barbara; Hart, T.K.; Feuerstein, G.; Elliott, John D.; Ohlstein, Eliot H.

doi:10.1161/01.res.75.1.190

Cited by 172 publications

(74 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Of particular interest in this connection, SB209670 strongly attenuated neointima formation following rat carotid artery balloon angioplasty (127,233). In angioplasty-induced neointima in rats, expressions of the mRNAs of endothelin-1, endothelin-3, ECE-1, ETA and ETB receptor were found to be increased (234).…”

Section: V-5 Vascular Thickeningmentioning

confidence: 93%

“…In addition to its acute vasoconstrictor effects, as already mentioned in the section on pulmonary hypertension, endothelin-1 is considered to exert chronic effects and to be deeply implicated in the proliferative responses associated with vascular diseases (221,222). Endothelin-1 has been reported to stimulate c fos, c jun and c-myc expression (223); increase the incorporation of [3H]-thymidine into DNA; and cause proliferation of vascular smooth muscle cells (224), capillary endothelial cells (225) and fibroblasts (226).…”

Section: V-5 Vascular Thickeningmentioning

confidence: 99%

See 1 more Smart Citation

Molecular Pharmacology and Pathophysiological Significance of Endothelin

Goto

Hama

Kasuya

1996

Japanese Journal of Pharmacology

159

108

View full text Add to dashboard Cite

ABSTRACT-Since the discovery of the most potent vasoconstrictor peptide, endothelin, in 1988, explosive investigations have rapidly clarified much of the basic pharmacological, biochemical and molecular biological features of endothelin, including the presence and structure of isopeptides and their genes (endothelin-1, -2 and -3), regulation of gene expression, intracellular processing, specific endothelia converting enzyme (ECE), receptor subtypes (ETA and ETB), intracellular signal transduction following receptor activation, etc. ECE was recently cloned, and its structure was shown to be a single transmembrane protein with a short intracellular N-terminal and a long extracellular C-terminal that contains the catalytic domain and numerous N-glycosylation sites. In addition to acute contractile or secretory actions, endothelin has been shown to exert long-term proliferative actions on many cell types. In this case, intracellular signal transduction appears to converge to activation of mitogen-activated protein kinase. As a recent dramatic advance, a number of non-peptide and orally active receptor antagonists have been developed. They, as well as current peptide antagonists, markedly accelerated the pace of investigations into the true pathophysiological roles of endogenous endothelin-1 in mature animals; e.g., hypertension, pulmonary hypertension, acute renal failure, cerebral vasospasm, vascular thickening, cardiac hypertrophy, chronic heart failure, etc. Thus, the interference with the endothelin pathway by either ECE-inhibition or receptor blockade may

show abstract

Section: V-5 Vascular Thickeningmentioning

confidence: 93%

Section: V-5 Vascular Thickeningmentioning

confidence: 99%

Molecular Pharmacology and Pathophysiological Significance of Endothelin

Goto

Hama

Kasuya

1996

Japanese Journal of Pharmacology

159

108

View full text Add to dashboard Cite

show abstract

“…13,14 Endothelin-1 levels are elevated after PTCA, suggesting that endothelin-1 is implicated in restenosis. In general, advanced atherosclerotic lesions are characterized by large numbers of smooth muscle cells, macrophages, and T lymphocytes.…”

Section: Endothelin and Neointima Formationmentioning

confidence: 99%

“…All animals treated with SB 209670 appeared healthy on gross physical examination, and there were no differences in body weights between treated rats and controls, indicating that the inhibitory effect of SB 209670 was not due to nonselective cytotoxicity. 14 Several studies have reported that cultured rat and human vascular smooth muscle proliferation is mediated by the ET A receptor. 15,16 Since endothelin-1 levels 14 are sharply elevated in the human coronary sinus after PTCA, it has been suggested that enhanced exposure of smooth muscle to endothelin-1 may stimulate neointima formation.…”

Section: Endothelin and Neointima Formationmentioning

confidence: 99%

“…14 Several studies have reported that cultured rat and human vascular smooth muscle proliferation is mediated by the ET A receptor. 15,16 Since endothelin-1 levels 14 are sharply elevated in the human coronary sinus after PTCA, it has been suggested that enhanced exposure of smooth muscle to endothelin-1 may stimulate neointima formation. Thus, endothelin-1 may be derived from circulating blood or come from damaged endothelial or smooth muscle cells in the vicinity of the lesion.…”

Section: Endothelin and Neointima Formationmentioning

confidence: 99%

See 1 more Smart Citation

Endothelin Inhibition as a Biologic Target for Treating Hypertension

Brunner

1998

American Journal of Hypertension

View full text Add to dashboard Cite

Endothelin, a 21-amino-acid peptide, binds to a specific receptor on vascular smooth muscle cells, thereby inducing vasoconstriction. Although plasma levels are not consistently elevated in hypertension, there is evidence that endothelin has an important role in its pathogenesis. Administration of endothelin antagonists has lowered blood pressure and reduced end-organ damage in some animal models. It has also reduced the cross-sectional area of neointima due both to hypertension and vascular injury. T he endothelium plays a role in regulating vascular resistance by releasing substances that dilate or constrict blood vessels. These substances, endothelins, are a family of peptides having potent vasoconstrictive effects. There are basically three types of endothelin: endothelin-1, endothelin-2, and endothelin-3. They are all formed from precursors (big endothelin) by enzymatic cleavage and are all 21-amino-acid peptides with disulfide bridges (Figure 1). Endothelin-1 and endothelin-2 act on the endothelin-A (ET A ) receptor of smooth muscle to produce a prolonged contraction and vasoconstriction. Endothelin-3 can also induce vasoconstriction by binding to the endothelin-B (ET B ) receptor on smooth muscle, but it also acts on the ET B receptors of endothelial cells, where it can actually have the opposite effect. It has been suggested that, under normal conditions, low concentrations of endothelin stimulate ET B receptors, thus contributing to the release of endothelium-derived relaxing factors. 1 Endothelin-1 is probably the best studied of this family. When administered to animals, endothelin-1 causes severe vasoconstriction. 2 The contraction of vascular smooth muscle produced by endothelin-1 may be mediated by an increase in intracellular calcium, but the details have not been established. 3 Infusion of endothelin-1 into healthy human volunteers resulted in a 2.5-fold increase in plasma endothelin-1 concentration and a rise

show abstract

Developmental toxicity and toxicokinetics of two endothelin receptor antagonists in rats and rabbits

et al. 1999

View full text Add to dashboard Cite

Embryo‐fetal development studies with toxicokinetic evaluations were conducted in rats and rabbits after oral or intravenous administration of two endothelin receptor antagonists. In the rat studies, females were administered SB‐217242 (0.01–300 mg/kg/day) orally or SB‐209670 (0.01–50 mg/kg/day) intravenously from days 6–17 postcoitus (pc). External and visceral fetal examinations were performed at necropsy on day 21 pc. Maternal body weight and food consumption were decreased only at 300 mg/kg/day SB‐217242. Embryolethality was seen at 300 mg/kg/day SB‐217242. Decreased fetal body weight occurred at 300 mg/kg/day SB‐217242 and 50 mg/kg/day SB‐209670. Dose‐dependent increases in the mean percentage of fetuses per litter with malformations were seen at ≥50 mg/kg/day SB‐217242 and ≥10 mg/kg/day SB‐209670. Craniofacial, great vessel, heart, and thyroid were the predominant malformations. In the rabbit studies, females were administered SB‐217242 (0.01–50 mg/kg/day) orally or SB‐209670 (0.01–25 mg/kg/day) intravenously from days 6–20 pc. There was no drug‐related effect on maternal body weight or food consumption. Embryolethality was observed at 50 mg/kg/day of SB‐217242. Dose‐related increases in the mean percentage of fetuses per litter with malformations were seen at ≥10 mg/kg/day SB‐217242 and ≥10 mg/kg/day SB‐209670. The malformations were similar to those observed in the rat studies, except that craniofacial development was not altered by SB‐209670. The malformations observed are consistent with the pattern of endothelin‐1 gene expression described in mouse embryonic pharyngeal arches and heart, and with the craniofacial and cardiovascular malformations observed in endothelin‐1‐deficient mice. Given the known role for endothelins in development, and concordant malformations in rats and rabbits observed in this study, teratogenicity is likely to be a class effect of endothelin receptor antagonists. Teratology 59:51–59, 1999. © 1999 Wiley‐Liss, Inc.

show abstract

A role for endogenous endothelin-1 in neointimal formation after rat carotid artery balloon angioplasty. Protective effects of the novel nonpeptide endothelin receptor antagonist SB 209670.

Cited by 172 publications

References 19 publications

Molecular Pharmacology and Pathophysiological Significance of Endothelin

Molecular Pharmacology and Pathophysiological Significance of Endothelin

Endothelin Inhibition as a Biologic Target for Treating Hypertension

Developmental toxicity and toxicokinetics of two endothelin receptor antagonists in rats and rabbits

Contact Info

Product

Resources

About