title: Anemoside A3-induced relaxation in rat renal arteries: role of endothelium and Ca2+ channel inhibition.
abstract: Anemoside A(3), a lupane-type triterpenoid saponin, exists in the roots of Pulsatilla chinensis, but its pharmacological properties are largely unknown. The present study aimed to investigate the mechanisms underlying anemoside A(3)-induced relaxation in rat renal arteries. Changes of isometric force were determined on arteries with a myograph. Anemoside A(3) caused concentration-dependent relaxation in precontracted aortas, mesenteric, left coronary, and renal arteries. Removal of endothelium or treatment with charybdotoxin plus apamin slightly but significantly attenuated the relaxation in renal arteries. TEA(+) inhibited the relaxation caused by anemoside A(3) in renal arteries with and without endothelium while glibenclamide, BaCl(2), or capsaicin had no effect on it. Anemoside A(3) produced less relaxation in rings contracted by 60 mM KCl compared with rings contracted by receptor-dependent constrictors. It further inhibited contractions induced by Ca(2+) influx through nifedipine-sensitive voltage-gated Ca(2+) channels, nifedipine-insensitive receptor-operated Ca(2+) channels, and by intracellular Ca(2+) release. Pretreatment with nifedipine attenuated anemoside A(3)-induced relaxation. Taken together, the present results indicate that anemoside A(3) produces relaxation in rat renal arteries through multiple mechanisms. The release of CTX/apamin-sensitive endothelium-derived hyperpolarizing factor, stimulation of TEA(+)-sensitive K(+) channel, and inhibition of Ca(2+) influx jointly contribute to the relaxation.
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, China.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Zhang
authors.forename: Shun-Ming
authors.initials: SM
authors.lastname: Lin
authors.forename: Chi-Wai
authors.initials: CW
authors.lastname: Lau
authors.forename: Anita
authors.initials: A
authors.lastname: Yiu
authors.forename: Jiao
authors.initials: J
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Fan
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.forename: Wen-Cai
authors.initials: WC
authors.lastname: Ye
mesh_terms: D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects; D001685:Biological Factors / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000302:isolation & purification / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009213:Myography; D009543:Nifedipine; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018517:Plant Roots; D015221:Potassium Channels / Q000187:drug effects; D011189:Potassium Chloride; D031946:Pulsatilla / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology*; D019789:Tetraethylammonium / Q000494:pharmacology; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D001685:Biological Factors; D002121:Calcium Channel Blockers; D010936:Plant Extracts; D015221:Potassium Channels; D012503:Saponins; D014315:Triterpenes; D014665:Vasodilator Agents; C473640:anemoside A3; C067410:endothelium-dependent hyperpolarization factor; D018999:Charybdotoxin; D001030:Apamin; D019789:Tetraethylammonium; D011189:Potassium Chloride; D009543:Nifedipine; D002211:Capsaicin; D005905:Glyburide; D002118:Calcium