Isosteviol ((-)-Isosteviol) dose-dependently relaxed the vasopressin (10 ^-8 M)-induced vasoconstriction in isolated aortic rings with or without endothelium. However, in the presence of potassium chloride (3×10 ^-2 M), the vasodilator effect of isosteviol on arterial strips disappeared. Only the inhibitors specific for the ATP-sensitive potassium (KATP) channel or small conductance calcium-activated potassium (SKCa) channel inhibited the vasodilator effect of isosteviol in isolated aortic rings contracted with 10 ^-8 M vasopressin.
The attenuation by isosteviol of the vasopressin- and phenylephrine-induced increase in [Ca ²⁺ ]i was inhibited by glibenclamide, apamin and 4-aminopyridine but not by charybdotoxin. Furthermore, the inhibitory action of isosteviol on [Ca ²⁺ ]i was blocked when A7r5 cells co-treated with glibenclamide and apamin in conjunction with 4-aminopyridine were present.
Isosteviol (1-100 micromol/l) inhibits angiotensin-II-induced DNA synthesis and endothelin-1 secretion. Measurements of 2'7'-dichlorofluorescin diacetate, a redox-sensitive fluorescent dye, showed an isosteviol-mediated inhibition of intracellular reactive oxygen species generated by the effects of angiotensin II.