The effects of palmatine on isometric force and intracellular free calcium levels ([Ca2+](i)) were determined in isolated rat arterial strips. Palmatine dose-dependently relaxed the contractile responses stimulated by phenylephrine (PE) in aortic strips. In contrast, it only partially relaxed aortic strips contracted by 51 mM KCl. Pretreatment with palmatine shifted the dose-response curves of PE both rightwards and downwards in a dose- dependent manner. When Ca2+-free solution and re-addition of Ca2+ were applied to assess PE-induced phasic and tonic contractions, palmatine was found to be effective in inhibiting both contractions. The effects of palmatine on intracellular calcium levels were measured with the bioluminescent calcium indicator aequorin in rat tail artery strips. Palmatine caused a concomitant, dose-dependent decrease in PE-activated isometric force and [Ca2+](i), resulting in small changes in the [Ca2+](i)-force relationship. These results suggest that vasodilatory effect of palmatine was mediated by reducing [Ca2+](i) as well as affecting [Ca2+](i) sensitivity of the contractile apparatus. Palmatine-induced [Ca2+](i) decreases appeared to involve decreases in both Ca2+ release from intracellular stores and Ca2+ influx through calcium channels.
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