Abstract
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 byS-petasin (0.1–100 μM), an action not affected by the cyclooxygenase inhibitor indomethacin, nitric-oxide synthase inhibitorNω-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.
Footnotes
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Send reprint requests to: Dr. Guei-Jane Wang, National Research Institute of Chinese Medicine, Rm. 355, 155-1, Sec. 2, Li-Nong St., Pei-tou Dist. (112), Taipei, Taiwan, Republic of China. E-mail:jennyw{at}cma23.nricm.edu.tw
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↵1 Current address: Department and Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, Republic of China.
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↵2 Current address: Heritage Medical Research Center, Cardiology of Medicine, University of Alberta, Edmonton, Alberta, Canada.
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↵3 Current address: Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine, Grand Forks, ND 58203.
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This work was supported by Grant NSC89-2320-B077-009 from the National Science Council of the Republic of China to G.J.W. Some information contained in this article was presented in preliminary form at the Experimental Biology 98 in San Francisco, CA (Wang et al., 1998).
- Abbreviations:
- NO
- nitric oxide
- VSMC
- vascular smooth muscle cell
- [Ca2+]i
- intracellular Ca2+concentration
- Fura-2/AM
- 1-[2-(5-carboxyoxazol-2-yl)-6-aminobenzofuran-5-oxy]-2-(2′-amino-5′-methylphenoxy)-ethane-N,N,N,N-tetraacetic acid pentaacetoxymethyl ester
- VDCC
- voltage-dependent Ca2+channel
- MAP
- mean arterial blood pressure
- l-NNA
- Nω-nitro-l-arginine
- I-V
- current-voltage
- Received November 6, 2000.
- Accepted January 3, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
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