Studies on the mechanism of antihypertensive action by nicotianamine

Nicotianamine (NA), which is obtained from vegetables, lowers blood pressure through the renin-angiotensin system, and we clarified that NA preferentially inhibits the activity of angiotensin I-converting enzyme (ACE)-a zinc-containing enzyme. In this study, we elucidated the mechanism of antihypertensive action of NA through the Magnus method by using rat aortic blood vessels. Angiotensin I-induced contractions were inhibited by NA in a concentration-dependant manner. Because NA did not inhibit angiotensin II-induced contractions, it was believed that NA inhibited ACE activity in vascular smooth muscles. NA did not affect KCl-induced contractions, but it affected norepinephrine-induced contractions to a small extent. NA exerted similar effects on endothelium-denuded and endothelium-intact blood vessels. Therefore, the antihypertensive action of NA did not play a role in the opening of voltage-dependent calcium channels, but this effect influenced vasoconstriction by the activation of α-adrenergic receptors. These results suggest that after absorption from the intestinal tract, NA may exert antihypertensive effects via 2 mechanisms: direct inhibition of ACE in vascular smooth muscle and activation of α-adrenergic receptors.