title: Vascular smooth muscle dysfunction and remodeling induced by ginsenoside Rg3, a bioactive component of ginseng.
abstract: Ginseng, one of most well-known herbal medicines, is widely and indiscreetly used among the patients with cardiovascular disorders, raising concern over abuse of this medicine and unwanted effects. In this study, we investigated the effects of ginsenoside Rg3 (Rg3), an active ingredient of ginseng, on vascular contractility and structural integrity to explore its potential vascular toxicity. In isolated rat aorta, Rg3 suppressed the normal agonist-induced contractile response. This suppression persisted even after a rigorous washout. In the endothelium-denuded aortic ring, impairment of vascular contractility by Rg3 was retained, suggesting that vascular smooth muscle was affected. In primary vascular smooth muscle cells, Rg3 abolished agonist-induced Ca(2+) increase, indicating that Ca(2+) regulation was disrupted. Rg3 suppressed the contraction induced by Bay K8644, an L-type Ca(2+) channel activator, whereas store-operated Ca(2+) channel or intracellular Ca(2+) store-mediated contraction was not affected, suggesting that the L-type Ca(2+) channel was selectively impaired by Rg3. These in vitro results were further confirmed in vivo where Rg3 treatment significantly attenuated the agonist-induced pressor response. More importantly, 4-week repeated treatment with Rg3 in normal animals induced eutrophic outward remodeling in the thoracic aorta, that is, it brought about an increased luminal area without changes in the wall area. These results suggest that Rg3 can induce the vascular smooth muscle dysfunction by disturbing Ca(2+) influx from the L-type Ca(2+) channel, ultimately leading to impaired vascular contractility and structural remodeling.
authors.affiliation: College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Kyung-Min
authors.initials: KM
authors.lastname: Lim
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Ok-Nam
authors.initials: ON
authors.lastname: Bae
authors.forename: Ji-Yoon
authors.initials: JY
authors.lastname: Noh
authors.forename: Seung-Min
authors.initials: SM
authors.lastname: Chung
authors.forename: Keunyoung
authors.initials: K
authors.lastname: Kim
authors.forename: Yoo-Sun
authors.initials: YS
authors.lastname: Shin
authors.forename: Moo-Yeol
authors.initials: MY
authors.lastname: Lee
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Chung
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects; D003600:Cytosol / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D036145:Ginsenosides / Q000633:toxicity*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000503:physiopathology; D009924:Organ Culture Techniques; D005894:Panax / Q000737:chemistry / Q000378:metabolism*; D010936:Plant Extracts / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
chemical_list: D020746:Calcium Channels, L-Type; D036145:Ginsenosides; D010936:Plant Extracts; C097367:ginsenoside Rg3; D002118:Calcium