The present study examined possible cellular mechanisms for the relaxation of rat renal arteries induced by Vindorosine extracted from C. roseus.
METHODS AND RESULTS:
Intrarenal arteries were isolated from 200-300 g male Sprague-Dawley rats and treated with different pharmacological blockers and inhibitors for the measurement of vascular reactivity on a Multi Myograph System. Fluorescence imaging by laser scanning confocal microscopy was utilized to determine the intracellular Ca(2+) level in the vascular smooth muscles of the renal arteries. Vindorosine in micromolar concentrations relaxes renal arteries precontracted by KCl, phenylephrine, 11-dideoxy-9α,11α-epoxymethanoprostaglandin F2α, and serotonin. Vindorosine-induced relaxations were unaffected by endothelium denudation or by treatment with the nitric oxide synthase inhibitor N (G)-nitro-L-arginine methyl ester hydrochloride, the guanylyl cyclase inhibitor 1H-[1, 2, 4]oxadiazolo[4,3-a]quinoxalin-1-one, the cyclooxygenase inhibitor indomethacin, or K(+) channel blockers such as tetraethylammonium ions, glibenclamide, and BaCl2. Vindorosine-induced relaxations were attenuated in the presence of 0.1 µM nifedipine (an L-type Ca(2+) channel blocker). Vindorosine also concentration-dependently suppressed contractions induced by CaCl2 (0.01-5 mM) in Ca-free 60 mM KCl solution. Furthermore, fluorescence imaging using fluo-4 demonstrated that 30 min incubation with 100 µM Vindorosine reduced the 60 mM KCl-stimulated Ca(2+) influx in the smooth muscles of rat renal arteries.
CONCLUSIONS:
The present study is probably the first report of blood vessel relaxation by Vindorosine and the possible underlying mechanisms involving the inhibition of Ca(2+) entry via L-type Ca(2+) channels in vascular smooth muscles. |
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