| Abstrakt: |
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 microM) 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 microM) or tetraethylammonium (TEA, 2 mM) did not significantly modify the vasorelaxant effects of this aporphine alkaloid. In the experiments in Ca(2+)-free medium, (+)-nantenine (10 microM) had no effect on caffeine-induced contractions. Furthermore, in the studies with radiolabelled Ca(2+), (+)-nantenine (3 - 30 microM) did not modify the basal uptake of (45)Ca(2+) but decreased, in a concentration-dependent fashion, the influx of (45)Ca(2+) induced by NA and KCl in endothelium-containing and endothelium-denuded rat aortic rings. In addition, (+)-nantenine (3 - 30 microM) was ineffective to scavenge superoxide anion (O(2) (-)) 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 Ca(2+) influx through transmembrane calcium channels, b) the activation of ATP-sensitive K(+) channels (K(ATP)) and large conductance Ca(2+)-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 O(2)(-) radicals scavenging properties are not involved in the vascular effects of (+)-nantenine in rat aorta described above. |
