The pharmacological effects on the cardiovascular system of
yangambin, a
lignan isolated from Ocotea duckei Vattimo (Lauraceae), were studied in rats using combined functional and biochemical approaches. In non-anaesthetized rats,
yangambin (1, 5, 10, 20, 30 mg/kg, i.v.)
induced hypotension (-3.5 ± 0.2; -7.1 ± 0.8; -8.9 ± 1.3; -14 ± 2.3, -25.5% ± 2.6%, respectively) accompanied by
tachycardia (5.9 ± 0.5; 5.9 ± 1.6; 8.8 ± 1.4; 11.6, 18.8% ± 3.4%, respectively). In isolated rat atria,
yangambin (0.1 µM-1 mM) had very slight negative inotropic (Emax = 35.6% ± 6.4%) and chronotropic effects (Emax = 10.2% ± 2.9%). In endothelium-intact rat mesenteric artery,
yangambin (0.1 µM-1 mM) induced concentration-dependent relaxation (pD2 = 4.5 ± 0.06) of contractions induced by
phenylephrine and this effect was not affected by removal of the endothelium. Interestingly, like
nifedipine, the relaxant effect induced by
yangambin was more potent on the contractile response induced by KCl 80 mM (pD2 = 4.8 ± 0.05) when compared to that induced by
phenylephrine. Furthermore,
yangambin inhibited CaCl2-induced contractions in a concentration-dependent manner. This
lignan also induced relaxation (pD2 = 4.0 ± 0.04) of isolated arteries pre-contracted with S(-)-
Bay K 8644. In
fura-2/AM-loaded myocytes of rat mesenteric arteries,
yangambin inhibited the Ca2+ signal evoked by KCl 60 mM. In conclusion, these results suggest that the hypotensive effect of
yangambin is probably due to a peripheral vasodilatation that involves, at least, the inhibition the Ca2+ influx through voltage-gated Ca2+ channels.