Preliminary Study of the Vasorelaxant Effects of (+)-Nantenine, an Alkaloid Isolated from Platycapnos spicata, in Rat Aorta

Abstract

In this work, the potential vasorelaxant activity of (+)-nantenine, an alkaloid isolated from Platycapnos spicata, was studied for the first time in rat aorta. (+)-Nantenine (3 - 30 μM) totally relaxed, in a concentration-dependent manner and with almost equal effectiveness, the contractions induced by noradrenaline (NA) or by a high KCl concentration (60 mM) in intact rat aortic rings. Mechanical removal of endothelium and/or pretreatment of aorta rings with glibenclamide (10 μM) or tetraethylammonium (TEA, 2 mM) did not significantly modify the vasorelaxant effects of this aporphine alkaloid. In the experiments in Ca²⁺-free medium, (+)-nantenine (10 μM) had no effect on caffeine-induced contractions. Furthermore, in the studies with radiolabelled Ca²⁺, (+)-nantenine (3 - 30 μM) did not modify the basal uptake of ⁴⁵Ca²⁺ but decreased, in a concentration-dependent fashion, the influx of ⁴⁵Ca²⁺ induced by NA and KCl in endothelium-containing and endothelium-denuded rat aortic rings. In addition, (+)-nantenine (3 - 30 μM) was ineffective to scavenge superoxide anion (O₂ ^-) radicals generated by the hypoxanthine (HX)-xanthine oxidase (XO) system and/or to inhibit XO activity. These results indicate that: a) the vasorelaxant effects of (+)-nantenine in rat aorta are due, at least in part, to a blockage of Ca²⁺ influx through transmembrane calcium channels, b) the activation of ATP-sensitive K⁺ channels (K_ATP) and large conductance Ca²⁺-activated K⁺ channels (K_Ca) present in smooth muscle cells, the presence (integrity) of endothelial system, an inhibitory action on XO enzymatic activity and/or O₂ ^- radicals scavenging properties are not involved in the vascular effects of (+)-nantenine in rat aorta described above.

Abbreviations

HX:hypoxanthine

IP₃:inositol 1,4,5-trisphosphate

K_ATP:ATP-sensitive K⁺ channels

K_Ca:large conductance Ca²⁺-activated K⁺ channels

NBT:nitro blue tetrazolium

NA:noradrenaline

NO:nitric oxide

OD:optical density

O₂ ^·-:superoxide anion

SOD:superoxide dismutase

TEA:tetraethylammonium

XO:xanthine oxidase

Vasorelaxant effects - rat aorta rings - calcium antagonist activity - (+)-nantenine - superoxide anions - xantine oxidase activity

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