ABSTRACT
Fructus Alpiniae Zerumbet (FAZ) is an herb widely used to treat vascular disorders in Guizhou province, China, the essential oil has been identified as one of it vasodilation effect active components, and especial, the composition was significantly difference from the leaves. Vasodilation effects and mechanism of essential oil from FAZ (EOFAZ) were investigated. The EOFAZ showed significant vasodilation effect on endothelium-with rat thoracic aortic rings preincubated with norepinephrine (NE, 1.0µM) or KCl (60mM) in a concentration-dependent manner (1.14-72.96µg/ml). The non-selective nitric oxide synthase inhibitor l-NAME, as well as the soluble guanylate cyclase inhibitor MB, attenuated the relaxation of EOFAZ in endothelium-intact rat thoracic aortic rings. However, there were not significantly affected the vasodilation effects pretreated with cyclooxygenase inhibition by indomethacin (Indo) or ß-noradrenergic inhibition by propranolol (Prop). The present results first demonstrated that vasodilation effect of EOFAZ depending upon the endothelium and concentration, and the mechanism involvement of NOS-cGMP system. In contrast, prostacyclin and ß-adrenoceptor may not be associated with EOFAZ-induced vasorelaxation.
Subject(s)
Aorta, Thoracic/drug effects , Endothelium-Dependent Relaxing Factors/pharmacology , Oils, Volatile/pharmacology , Zingiberaceae/chemistry , Animals , Drug Evaluation, Preclinical , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Endothelium, Vascular/drug effects , Endothelium-Dependent Relaxing Factors/chemistry , Endothelium-Dependent Relaxing Factors/isolation & purification , Guanylate Cyclase/antagonists & inhibitors , In Vitro Techniques , Indomethacin/pharmacology , Male , Muscle Relaxation , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Oils, Volatile/chemistry , Oils, Volatile/isolation & purification , Propranolol/pharmacology , Rats , Rats, Sprague-DawleyABSTRACT
Hyperosmolar challenge of airway epithelium stimulates the release of epithelium-derived relaxing factor (EpDRF), but the identity of EpDRF is not known. We examined the effects of pharmacological agents on relaxant responses of methacholine (3 x 10(-7) M)-contracted guinea pig perfused trachea to mucosal hyperosmolar challenge using D-mannitol. Responses were inhibited by gossypol (5 x 10(-6) M), an agent with diverse actions, by the carbon monoxide (CO) scavenger hemoglobin (10(-6) M), and by the heme oxygenase (HO) inhibitor zinc (II) protoporphyrin IX (10(-4) M). The HO inhibitor chromium (III) mesoporphyrin IX (10(-4) M) was not inhibitory, and the HO activator heme-L-lysinate (3 x 10(-4) M) did not evoke relaxant responses. The CO donor tricarbonyldichlororuthenium (II) dimer (2.2 x 10(-4) M) elicited small relaxation responses. Other agents without an effect on responses included: apyrase, adenosine, 6-anilino-5,8-quinolinequinone (LY83583), proadifen, (E)-3-[[[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl][[3-(dimethylamino)-3-oxopropyl]thio]methyl]thio]-propanoic acid (MK 571), diphenhydramine, glibenclamide, HgCl2, tetrodotoxin, nystatin, alpha-hemolysin, 8-bromoguanosine 3',5'-cyclic monophosphothioate, Rp-isomer, 12-O-tetradecanoylphorbol-13-acetate, cholera toxin, pertussis toxin, thapsigargin, nifedipine, Ca(2+)-free mucosal solution, hydrocortisone, and epidermal growth factor. Cytoskeleton inhibitors, includingerythro-9-(2-hydroxyl-3-nonyl)adenine, colchicine, nocodazole, latrunculin B, and cytochalasins B and D, had no effect on relaxation responses. The results suggest provisionally that a portion of EpDRF activity may be due to CO and that the release of EpDRF does not involve cytoskeletal reorganization.
