1-Nitro-2-phenylethane (NPE), a hypotensive substance found in the essential oil of
Aniba canelilla, has vasodilator properties. Here, the underlying mechanism of such effect was studied
in rings of rat aorta under isometric recording conditions. In endothelium-intact
aortic rings, NPE (1–300µg/mL) relaxed the phenylephrine (PHE)-induced contractions
with IC50 values of 35.0 [23.3–52.6] µg/mL, effect significantly (n=22, P<0.05, Mann-Whitney)
decreased by ODQ (10µM, n=6) or methylene blue (10µM, n=9) but not by endothelium
removal (n=7) or by pretreatment with L-NAME (100µM, n=6), indomethacin (10µM, n=6),
MDL-12,330A (3µM, n=7), KT5823 (0.5µM, n=7) or KT5720 (1µM, n=8). In Ca2+-free medium, in presence of K+ (60 mM, n=10) or PHE (1µM, n=7), CaCl2-induced contractions were almost abolished by NPE at 100µg/mL. In Ca2+-free medium, containing EGTA, the contractile response of PHE was significantly reduced
by NPE (100µg/mL, n=6), an effect prevented by treatment with ODQ (10µM, n=6) and
was inert on caffeine-induced contraction (n=6). Similar results were obtained with
sodium nitroprusside (n=6). In silico (docking) simulation revealed clusters of interactions
of NPE with the guanylate cyclase molecule. Thus, the vasorelaxant activity of NPE
on rat aorta appears due to its stimulatory properties on guanylate cyclase.