Ca2+ channel blocking effects of hirsutine, and indole alkaloid from Uncaria genus, in the isolated rat aorta

Abstract Ca 2+ channel blocking activity of hirsutine and its pharmacological features were studied. Hirsutine (10 -6 to 3 × 10 -5 M) produced a dose-dependent relaxation of the isolated rat aorta contracted by norepinephrine and high K + concentration. This effect was exhibited in the aorta strips with or without the endothelium, suggesting an involvement of vasodilative mechanisms not dependent on the endothelium. Hirsutine also inhibited the contractions induced by serotonin and Ca 2+ channel activator YC-170, but not by Ca 2+ ionophore A23187. The pA 2 value of hirsutine was 6.6 ± 0.1 (mean ± S.E.; n = 4) in antagonizing cumulative dose-response curve for Ca 2+ in the depolarized aorta strips. It is concluded that hirsutine apparently exhibits Ca 2+ channel blocking activity mainly through inhibition of the voltage-dependent Ca 2+ influx.