Wang Y P, Chen W Z, Gu P K
Shanghai Institute of Materia Medica, Chinese Academy of Sciences.
Zhongguo Yao Li Xue Bao. 1990 Nov;11(6):502-5.
Guan-fu base A (GFA) is a new alkaloid isolated from the tuber of Aconitum coreanum in our institute. Its effects on spontaneous electrical discharge rate of intact sinoatrial node preparations were investigated. Unipolar Ag-AgCl2 electrodes and DC-amplification were used to record unipolar electrograms from the endocardial surface of the isolated right guinea pig atria. GFA (4.29-214.5 micrograms/ml) decreased the spontaneous electrical discharge rate of sinoatrial node in a dose-dependent manner. The most effective concentration (214.5 micrograms/ml) of GFA resulted in sinus rate of 115 +/- 8 bpm (n = 7, control rate 208 +/- 13 bpm) within 30 min. Low external Ca2+ (0.18 mmol/L) enhanced the rate in lowering effect of GFA, in contrast with high external K+ (10.8 mmol/L) diminishing the effect of GFA. The ratios of IC30 of negative inotropic effects over IC30 of negative chronotropic effects were 9.38 for GFA and 1.73 for verapamil. GFA antagonized the positive chronotropic effect of isoproperenol but did not antagonize the positive inotropic effect of isoproterenol. The consequence of lowering sinus rate by GFA was not interfered by propranolol (0.15 micrograms/ml) or atropine (0.05 micrograms/ml). These results suggest that the bradycardia by GFA is a direct effect on sinoatrial node, but not due to the calcium channel block or beta adrenoceptor block.
关附甲素(GFA)是我们研究所从朝鲜乌头块根中分离出的一种新生物碱。研究了其对完整窦房结标本自发放电率的影响。使用单极银 - 氯化银电极和直流放大技术记录分离的豚鼠右心房心内膜表面的单极电图。GFA(4.29 - 214.5微克/毫升)以剂量依赖性方式降低窦房结的自发放电率。GFA最有效浓度(214.5微克/毫升)在30分钟内使窦性心率降至115±8次/分钟(n = 7,对照心率208±13次/分钟)。低细胞外钙(0.18毫摩尔/升)增强了GFA的降心率作用,而高细胞外钾(10.8毫摩尔/升)则减弱了GFA的作用。GFA负性变力作用的IC30与负性变时作用的IC30之比为9.38,维拉帕米为1.73。GFA拮抗异丙肾上腺素的正性变时作用,但不拮抗异丙肾上腺素的正性变力作用。普萘洛尔(0.15微克/毫升)或阿托品(0.05微克/毫升)不干扰GFA降低窦性心率的作用。这些结果表明,GFA引起的心动过缓是对窦房结的直接作用,而非由于钙通道阻滞或β肾上腺素能受体阻滞。