Comparative effects of some naturally-occurring aspidofractinine-type alkaloids on the blood pressure in spontaneously hypertensive rats
2000
Choo, Y.M. | Kok, L.K. | Lim, T.M. | Mok, S.L. | Subramaniam, G. | Kam, T.S.
The effect of saveral aspidofractinine-type alkaloids derived from the genus kopsia (Apocynacea) on the mean arterial blood pressure (MABP) were examined in anaesthetised male spontaneously hypertensive rats (SHR) of the japanese strain. The alkaloids investigated are kopsingine, kopsaporine and kopsidine A from K, teoi, kopsamine and methyl 11,12- methylenedioxychanofruiticosinate from K. dasyrachis. Intravenous (i.v) injections of 0.2-10.0mg/kg of kopsingine, kopsaporine, kopsamine and methyl 11,12-methyleneddioxychanofruiticosinate produced liner dose- related decreases in MABP. After attaining a peak within the initial 10 to 30 s` the values returned to predrug levels during the following 3 to 5 min., and these were accompanied by bradycardia in all the rats tested. In contrast,kopsidine A (0.2 to 10.0mg/kg) produced a small, dose-related increase in MABP and decrease in heart rate (HR) after i.v injection pretreatment with atropine (2 mg/kg),phentolamine (3mg/kg) and hexamethonium (20 mg/kg) on the cardiovasscular effects of 10 mg/kg of i.v. injection of these alkaloids were also studied. Atropine was ineffective in antagonising the cardiovascular responses to kopsigine and kopsamine in SHR. The depressor actions of kopsingine were significantly attenuated by hexamethonium, but completely reversed to pressor actions by phentolamine. Both the depressor and bradycardic effects of kopsamine were significantly reduced by phentolamine. Our results show that only the indole alkaloids devoid of the 3-to17 oxo-bridge in the aspidofractinine molecular skeleton could effectively lower the arterial pressure. The antihypertensive effects of kopsingine and its congeners along with the pressor effect produced by kopsidine A could be ascribed to central as well as peripheral actions.
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