Candesartan ameliorates arsenic-induced hypertensive vascular remodeling by regularizing angiotensin II and TGF-beta signaling in rats

Highlights • Examined whether candesartan can ameliorate arsenic-induced vascular disorders. • Arsenic caused systemic hypertension & also enhanced AngII-induced blood pressure. • Arsenic elevated AngII & TGF-β levels; up-regulated aortic AT1 & TβRII receptors. • Also increased transduce...

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Veröffentlicht in:	Toxicology (Amsterdam) 2016-12, Vol.374, p.29-41
Hauptverfasser:	Khuman, Maibam Wanta, Harikumar, Sankaran Kutty, Sadam, Abdul, Kesavan, Manickam, Susanth, Vattaparambil Sukumaran, Parida, Subhashree, Singh, Karam Pal, Sarkar, Souvendra Nath
Format:	Artikel
Sprache:	eng
Schlagworte:	Angiotensin II Angiotensin II - metabolism Angiotensin II Type 1 Receptor Blockers - therapeutic use Animals Aorta, Thoracic - pathology Arsenic Arsenic Poisoning - drug therapy Arsenic Poisoning - pathology Arsenites - antagonists & inhibitors Arsenites - toxicity Benzimidazoles - therapeutic use Blood Pressure - drug effects Candesartan Collagen - metabolism Collagens Deposition Dose-Response Relationship, Drug Emergency Exposure Fibrosis - pathology Hypertension Kinases Male Rats Rats, Wistar Receptors Remodeling Signal Transduction - drug effects Signaling Smad Proteins - metabolism Sodium Compounds - antagonists & inhibitors Sodium Compounds - toxicity Tetrazoles - therapeutic use TGF-β Transforming Growth Factor beta - metabolism Vascular fibrosis Vascular Remodeling - drug effects
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Zusammenfassung:	Highlights • Examined whether candesartan can ameliorate arsenic-induced vascular disorders. • Arsenic caused systemic hypertension & also enhanced AngII-induced blood pressure. • Arsenic elevated AngII & TGF-β levels; up-regulated aortic AT1 & TβRII receptors. • Also increased transducers of MAPK & TGF-β pathways, aortic collagen & thickness. • Candesartan reduced arsenic-induced functional, biochemical & structural changes.
ISSN:	0300-483X 1879-3185
DOI:	10.1016/j.tox.2016.11.015