title: Synergistic Antihypertensive Effect of Carthamus tinctorius L. Extract and Captopril in L-NAME-Induced Hypertensive Rats via Restoration of eNOS and AT₁R Expression.
abstract: This study examined the effect of Carthamus tinctorius (CT) extract plus captopril treatment on blood pressure, vascular function, nitric oxide (NO) bioavailability, oxidative stress and renin-angiotensin system (RAS) in N(ω)-Nitro-l-arginine methyl ester (l-NAME)-induced hypertension. Rats were treated with l-NAME (40 mg/kg/day) for five weeks and given CT extract (75 or 150 or 300 or 500 mg/kg/day): captopril (5 mg/kg/day) or CT extract (300 mg/kg/day) plus captopril (5 mg/kg/day) for two consecutive weeks. CT extract reduced blood pressure dose-dependently, and the most effective dose was 300 mg/kg/day. l-NAME-induced hypertensive rats showed abnormalities including high blood pressure, high vascular resistance, impairment of acetylcholine-induced vasorelaxation in isolated aortic rings and mesenteric vascular beds, increased vascular superoxide production and plasma malondialdehyde levels, downregulation of eNOS, low level of plasma nitric oxide metabolites, upregulation of angiotensin II type 1 receptor and increased plasma angiotensin II. These abnormalities were alleviated by treatment with either CT extract or captopril. Combination treatment of CT extract and captopril normalized all the abnormalities found in hypertensive rats except endothelial dysfunction. These data indicate that there are synergistic antihypertensive effects of CT extract and captopril. These effects are likely mediated by their anti-oxidative properties and their inhibition of RAS.
authors.affiliation: Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. pumaneesai@hotmail.com.
authors.forename: Putcharawipa
authors.initials: P
authors.lastname: Maneesai
authors.affiliation: Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. unicorn_fang-19@hotmail.com.
authors.forename: Patoomporn
authors.initials: P
authors.lastname: Prasarttong
authors.affiliation: Faculty of Medical Sciences, Nakhonratchasima College, Nakhonratchasima 30000, Thailand. bugvo@hotmail.com.
authors.forename: Sarawoot
authors.initials: S
authors.lastname: Bunbupha
authors.affiliation: Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. upa_ku@kku.ac.th.
authors.forename: Upa
authors.initials: U
authors.lastname: Kukongviriyapan
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. veerapol@kku.ac.th.
authors.forename: Veerapol
authors.initials: V
authors.lastname: Kukongviriyapan
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. pantan@kku.ac.th.
authors.forename: Panot
authors.initials: P
authors.lastname: Tangsucharit
authors.affiliation: Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. prapra@kku.ac.th.
authors.forename: Parichat
authors.initials: P
authors.lastname: Prachaney
authors.affiliation: Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. ppoung@kku.ac.th.
authors.forename: Poungrat
authors.initials: P
authors.lastname: Pakdeechote
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology*; D031187:Carthamus tinctorius / Q000737:chemistry*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects* / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D010936:Plant Extracts; D044140:Receptor, Angiotensin, Type 1; D009569:Nitric Oxide; D002216:Captopril; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019331:NG-Nitroarginine Methyl Ester
keywords: ">l-NAME-induced hypertension; Carthamus tinctorius L.; captopril; eNOS expression; oxidative stress; renin-angiotensin system