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Cellular calcium regulatory machinery of vasorelaxation elicited by petasin.

Abstract：

:1. The present study examined the cytosolic Ca(2+) regulatory machinery involved in the vasorelaxation produced by petasin, a sesquiterpene isolated from Petasites formosanus. 2. Aortic rings isolated from Sprague-Dawley rats were exposed to petasin (0.01-100 micromol/L) to elucidate its vascular effects on isometric contraction elicited by vasoconstrictors, as well as the contribution of the endothelium and Ca(2+) to the responses observed. In addition, L-type voltage-dependent Ca(2+) channel (VDCC) activity and [Ca(2+)](i) were determined in cultured vascular smooth muscle cells (VSMCs) from Sprague-Dawley rats in the presence of 1-100 micromol/L petasin using whole-cell patch-clamp recording and the fluorescent probe fura-2/AM. The effects of petasin on vascular responses were compared between aortic rings from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. 3. Petasin reduced isometric contraction elicited by KCl or the L-type Ca(2+) channel opener BayK 8644 (IC(50) 3.0 +/- 0.4 and 4.1 +/- 1.1 micromol/L, respectively) in aortic rings isolated from Sprague-Dawley rats, independent of the endothelium. In addition, petasin triggered a rightward shift in the concentration-response curve to KCl while reducing the maximal response by 82%. In Ca(2+)-depleted and high K(+)-depolarized aortic rings, 1-100 micromol/L petasin pretreatment attenuated the Ca(2+)-induced contraction in a concentration-dependent manner. 4. In cultured VSMCs, whole-cell patch-clamp recording revealed that petasin inhibited VDCC activity. Measurement of [Ca(2+)](i) using fura-2/AM fluorescence indicated that petasin suppressed the KCl-induced increase in [Ca(2+)](i). However, receptor binding assays failed to identify any significant interaction between petasin and the dihydropyridine binding sites of the L-type VDCC. 5. In aortic rings from SHR and WKY rats, petasin inhibited Ca(2+)-induced contractions in Ca(2+)-depleted and high K(+)-depolarized solution with a more pronounced effect in rings from SHR. 6. Together, the results suggest that direct Ca(2+) antagonism of L-type VDCC in vascular smooth muscle may account, at least in part, for petasin-induced vasorelaxation. The more pronounced effect of the sesquiterpene in blood vessels from SHR suggests its possible therapeutic potential in the mangement of hypertension.

journal_name

Clin Exp Pharmacol Physiol

journal_title

Clinical and experimental pharmacology & physiology

authors

Wang GJ,Lin YL,Chen CH,Wu XC,Liao JF,Ren J

doi

10.1111/j.1440-1681.2009.05283.x

subject

Has Abstract

pub_date

2010-03-01 00:00:00

pages

309-15

issue

eissn

0305-1870

issn

1440-1681

pii

CEP5283

journal_volume

pub_type

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Cellular calcium regulatory machinery of vasorelaxation elicited by petasin.