Background　We previously reported that a food containing an extract from long pepper which included piperine（90μg）exhibited an antihypertensive effect, in the study that was conducted in individuals with blood pressure in the high normal range and patients with first- degree hypertension. A significant reduction of both the systolic and diastolic blood pressures was observed, beginning from early as 1 week after the start of intake in 12-week continuous intake study.
Objectives　This study sought to clarify the mechanism of action for the hypotensive effects of piperine.
Methods　We evaluated the inhibitory effects of piperine on the pressor response using angiotensin I（ AT I）in rats. Next, the vasorelaxant effects of piperine were evaluated in the isolated rat aortic ring strips contracted with phenylephrine（PE）and the involvement of vascular endothelial cells and nitric oxide synthase（NOS）were examined. Finally, we also evaluated the increase in intracellular nitric oxide（NO）levels after treatment with piperine in human aortic endothelial cells.
Results　Piperine（11.25 mg/kg）significantly suppressed the elevation in blood pressure induced by AT I. Piperine（10-100μmol/L）also significantly inhibited the PE-induced contraction of rat aortic strips in a concentration―dependent manner, and the vasodilation effects of piperine were inhibited by the removal of the endothelium or pretreatment with a NOS inhibitor. Moreover, piperine（30, 100μmol/L）significantly increased the intracellular NO level.
Conclusions　These results suggest that piperine reduces blood pressure by inducing vasodilation through increased NO production.