The antihypertensive effect of stevioside derivative isosteviol in spontaneously hypertensive rats

Background: Hypertension is one of the most common disease entity causing major mortality. Isosteviol (IST) is the derivative from stevioside. Stevioside is a sweet-tasting glycoside existed in the leaves of the herb Stevia rebaudiana that has been using widely in Japan as sugar substitute. Stevioside has been proved to have hypotensive effect. This study investigated the antihypertensive effect of isosteviol in spontaneously hypertensive rats (SHR). Methods: Isosteviol synthesized from stevioside was employed to inject intraperitoreally into SHR by dose-dependent manner. Isolated aortic strips and vascular smooth muscle cells were employed to evaluate the mechanism of hypotension. Results: IST (25 mg/kg) given intraperitoneally decreased mean artery blood pressure by 12 mmHg. In isolated aortic rings from rats, IST could dose-dependently relaxed vasopressin-induced vasoconstriction. IST had no effect on phenylephrine- induced vasoconstriction that produced mainly due to intracellular calcium (Ca2+) release. Also, IST failed to modify the vasopressin-induced vasoconstriction in Ca2+-free medium. The results indicate that IST has vasorelaxatory effect via an inhibition of Ca2+ influx. Reduction in the vasopressin-induced vasoconstriction by IST was also obtained in the absence of endothelium, showing this pharmacological effect of IST was not related to nitric oxide and/or endothelium system. Conclusions: Isosteviol (IST) the new derivative from stevioside, has remarkable antihypertensive effect as its parent compound in SHR. The mechanism of hypotension is probably through calcium influx inhibition in vascular smooth muscle cells.