Vol. 297, Issue 1, 240-246, April 2001

Calcium Channel Blockade in Vascular Smooth Muscle Cells: Major Hypotensive Mechanism of S-Petasin, a Hypotensive Sesquiterpene from Petasites formosanus

Guei-Jane Wang, Andrew Yau-Chik Shum¹, Yun-Lian Lin, Jyh-Fei Liao¹, Xi-Chen Wu², Jun Ren³ and Chieh-Fu Chen

National Research Institute of Chinese Medicine, Taipei, Taiwan, Republic of China

In vivo and in vitro studies were carried out to examine the putative hypotensive actions of S-petasin, a sesquiterpene extracted from the medicinal plant Petasites formosanus. Intravenous S-petasin (0.1-1.5 mg/kg) in anesthetized rats produced a dose-dependent hypotensive effect. In isolated aortic ring, isometric contraction elicited by KCl or the L-type Ca²⁺ channel agonist Bay K 8644 was reduced by S-petasin (0.1-100 µM), an action not affected by the cyclooxygenase inhibitor indomethacin, nitric-oxide synthase inhibitor N-nitro-L-arginine, guanylyl cyclase inhibitor methylene blue, or removal of vascular endothelium. Pretreatment with S-petasin for 10 min shifted the concentration-response curve for KCl (15-90 mM)-induced contraction to the right and reduced the maximal response. In Ca²⁺-depleted and high K⁺-depolarized aortic rings preincubation with S-petasin attenuated the Ca²⁺-induced contraction in a concentration-dependent manner, suggesting that S-petasin reduced Ca²⁺ influx into vascular smooth muscle cells (VSMCs). Moreover, in cultured VSMCs, whole-cell patch-clamp recording indicated that S-petasin (1-50 µM) inhibited the L-type voltage-dependent Ca²⁺ channel (VDCC) activities. Intracellular Ca²⁺ concentration ([Ca²⁺]_i) estimation using the fluorescent probe 1-[2-(5-carboxyoxazol-2-yl)-6-aminobenzofuran-5-oxy]-2-(2'-amino-5'-methylphenoxy)-ethane-N,N,N,N-tetraacetic acid pentaacetoxymethyl ester indicated that S-petasin (10, 100 µM) suppressed the KCl-stimulated increase in [Ca²⁺]_i. Taken together, the results suggested that a direct Ca²⁺ antagonism of L-type VDCC in vascular smooth muscle may account, at least in part, for the hypotensive action of S-petasin.