Vasorelaxation induced by 1-Nitro-2-Phenylethane in rat aorta involves guanylate cyclase stimulation
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.