RESUMO
AIM: To study the effects of osthole (Ost) on the isolated guinea pig atria and the relationship between Ost effect and Ca2+. METHODS: Contractions of left atria were induced by electric stimulations. The contractile amplitude of left atria pre- and post-treated with Ost was measured according to the cumulative concentration method, the drug being added at 15 min intervals, the pA2 or pD2' were calculated. It were measured that the effects of Ost to the positive staircase and to the post-rest potential enhancement. The contractile responses were recorded via an auto-equiolibration recording instrument. RESULTS: Ost 10-300 mumol.L-1 and Ver 0.1-30 mumol.L-1 decreased the contractile force and inhibited the isoprenaline-induced restoration of contractile response in the left atria rendered inexcitable by KCl 25 mmol.L-1. Ost and Ver antagonized the CaCl2- and isoprenaline-induced positive inotropic response noncompetively, the pD2' values to Ost were 4.41 +/- 0.13 and 4.90 +/- 0.15, to Ver were 6.53 +/- 0.22 and 6.91 +/- 0.17, respectively. Both of them inhibited the contraction of the left atrium and reversed the frequency-contraction response from positive to negative staircase in the higher dosage (500 and 1 mumol.L-1), but they showed only slight inhibitory effect on post-rest potentiation. CONCLUSION: Ost was similar to, but much less potent than Ver in inhibiting the isolated guinea pig atria.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Cumarínicos/farmacologia , Contração Miocárdica/efeitos dos fármacos , Animais , Cloreto de Cálcio/antagonistas & inibidores , Cumarínicos/isolamento & purificação , Depressão Química , Cobaias , Átrios do Coração/efeitos dos fármacos , Técnicas In Vitro , Isoproterenol/antagonistas & inibidores , Masculino , Plantas Medicinais/química , Verapamil/farmacologiaRESUMO
Effects of osthole (Ost) and verapamil (Ver) were investigated in the isolated guinea-pig ileum and taeniae coli. In the isolated guinea-pig ileum or taeniae coli, Ost and Ver were both found to inhibit the contractions induced by acetylcholine (ACh), histamine (His) and KCl in a dose-dependent manner; and noncompetitively antagonize the CaCl2 cumulative dose-response curves, with pD2 values of 4.41 +/- 0.15 and 7.0 +/- 0.2, respectively. Ost at dose of 100 mumol/L and Ver at 1 mumol/L inhibited CaCl2 0.2 mmol/L induced the contractions of the isolated guinea-pig taeniae coli, and the contractions can be abolished by adding CaCl2 2 mmol/L in Ca(2+)-free medium; both of them showed pronounced inhibitions on intracellular calcium-dependent contractions induced by ACh, but showing no effects on the extracellular calcium-dependent contractions. These results indicate that Ost has calcium antagonistic effect and is similar to Ver in mechanism.
