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.

The contributions of muscarinic receptors and changes in plasma aldosterone levels to the anti-hypertensive effect of Tulbaghia violacea

“…An average of 5 consecutive readings was recorded. Rats were trained every 3 days for BP measurement for two weeks prior to the start of the actual experiment [26-29]. …”

“…The SHRs used in this protocol were allowed 14 days of acclimatization to the restrainers [26-29]. The body weight, SBP and HR of the rats were measured on the first day of study, and the rats were randomly divided into three groups of eight each.…”

Calcium blockers inhibit cyclosporine A-induced hyperreactivity of vascular smooth muscle cells

“…Apart from vasoconstriction action, BayK-8644 may exert inotropic effects (31). CsA did not increase the reactivity of arteries on the pressor action of BayK-8644.…”

Phytochemical, pharmacological and clinical studies of petasites hybridus (l.) P. Gaertn., B. Mey. & Scherb. A review /

“…Recently, Wang et al [77] examined the cytosolic Ca 2+ regulatory mechanism involved in the vasorelaxation induced by petasin (from P. formosanus) at a concentration 0.01-100 µmol/l. In this study, cultured vascular smooth muscle cells, aortic rings from Sprague-Dawley rats, spontaneously hypertensive rats and normotensive Wistar-Kyoto rats were used.…”