title: Nitric oxide signalling is involved in diarylheptanoid-induced increases in femoral arterial blood flow in ovariectomized rats.
abstract: The mechanisms by which the hexane extract of Curcuma comosa increases femoral blood flow (FBF) in ovariectomized rats are not known. Thus, the aim of the present study was to investigate the acute effects and modes of action of the diarylheptanoid (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (D3), a phyto-oestrogen isolated from C. comosa, on FBF in ovariectomized rats. On Day 7 after ovariectomy, rats were injected once intra-arterially with D3 (100, 200, 400 and 800 μg/kg), 17β-oestradiol (E2; 1, 2, 4 and 8 μg/kg) or vehicle. In some experiments, rats were injected with N(G)-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg) 120 min after 800 μg/kg D3 or 4 μg/kg E2. In other experiments, rats were injected with 10 mg/kg L-NAME, 900 μg/kg 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or 900 μg/kg ICI 182 780 30 min prior to the injection of 800 μg/kg D3 or 4 μg/kg E2. Mean arterial blood pressure (mABP) and FBF were recorded using a pressure transducer and a laser Doppler flow meter, respectively. Both D3 and E2 dose-dependently increased FBF without changing mABP or heart rate. The EC(50) at 120 min for D3 and E2 was 195.8 and 1.8 μg/kg, respectively. In addition, D3 and E2 dose-dependently decreased femoral vascular resistance (FVR). The EC(50) of D3 was about 100-fold greater than that of E2. The effects of D3 and E2 on FBF and FVR were diminished by intravenous injection of 10 mg/kg l-NAME. Furthermore, 30 min pretreatment with L-NAME (10 mg/kg), ODQ (900 μg/kg) or ICI 182 780 (900 μg/kg) blocked the effects of D3 and E2 on FBF and FVR. The results of the present study suggest that the phyto-oestrogen D3 increases FBF in ovariectomized rats via oestrogen receptor and nitric oxide-guanylyl cyclase signalling, which, in turn, relaxes femoral vascular resistance.
authors: Department of Physiology, Faculty of Science, Mahidol University,Bangkok, Thailand.
authors: Ganyapong
authors: G
authors: Chaturapanich
authors: Rungsima
authors: R
authors: Yamthed
authors: Pawinee
authors: P
authors: Piyachaturawat
authors: Arthit
authors: A
authors: Chairoungdua
authors: Wisuda
authors: W
authors: Suvitayavat
authors: Boontium
authors: B
authors: Kongsaktrakoon
authors: Apichart
authors: A
authors: Suksamrarn
authors: Chumpol
authors: C
authors: Pholpramool
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects* / Q000502:physiology; D030024:Curcuma / Q000737:chemistry*; D036381:Diarylheptanoids; D004305:Dose-Response Relationship, Drug; D005260:Female; D005263:Femoral Artery / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006162:Guanylate Cyclase / Q000096:biosynthesis; D019850:Heptanol / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D007269:Injections, Intra-Arterial; D015394:Molecular Structure; D009569:Nitric Oxide / Q000096:biosynthesis*; D010052:Ovariectomy; D048789:Phytoestrogens / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects*; D015398:Signal Transduction; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: C558048:1,7-diphenyl-4,6-heptadien-3-ol; D036381:Diarylheptanoids; D048789:Phytoestrogens; D009569:Nitric Oxide; D019850:Heptanol; D006162:Guanylate Cyclase