A novel in vitro endothelium-dependent vascular relaxant effect of Apocynum venetum leaf extract.
1. In the present study, a novel in vitro vascular relaxant effect of Apocynum venetum leaf extract (AVLE; also called 'Luobuma'), obtained from a traditional Chinese medicinal herb with known antihypertensive effects, is reported in isometric contraction studies of rat aorta and superior mesenteric artery. At low concentrations (0.3-10 microg/mL), AVLE had no effect on the resting tension of either blood vessel and caused relaxation in agonist-precontracted vessels with functionally intact endothelium. 2. We demonstrated pharmacologically that the AVLE-induced vasorelaxation was mediated selectively by the endothelial cells in both blood vessels. Using NG-nitro-L-arginine methyl ester (L-NAME) and a low concentration of KCl (15 mmol/L), we also demonstrated that AVLE acted by releasing endothelium-derived relaxation factors; nitric oxide (NO) in the rat aorta and NO plus endothelium-derived hyperpolarizing factor in the rat mesenteric artery. 3. The vascular relaxation following brief exposure to AVLE appeared to persist even after subsequent prolonged washout; this was manifested as an attenuated contraction to subsequent application of phenylephrine (PE) compared with the PE-induced contraction after exposure to carbachol (CCh) and subsequent similar washout. The addition of L-NAME at this point in the absence of AVLE totally restored the contraction to PE, suggesting that enzymatic generation of endothelial NO persisted even after brief exposure to AVLE. 4. Unlike the endothelium-dependent NO-mediated relaxation induced by CCh, which is mediated by endothelial muscarinic receptors (and inhibited by atropine), the relaxation induced by AVLE was not inhibited by atropine and, thus, was not mediated by muscarinic receptors. However, similar to CCh-induced relaxation, AVLE-induced relaxation was associated with the activation of K+ channels. 5. These results provide a strong scientific basis for the folk use of AVLE decoction for antihypertensive therapy in traditional Chinese medicine.
Kwan
Chiu-Yin
CY
Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada. kwancy@univmail.mcmaster.ca
Zhang
Wen-Bo
WB
Nishibe
Sansei
S
Seo
Shujiro
S
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D030010:Apocynum / Q000737:chemistry*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D004365:Drugs, Chinese Herbal; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid