Hypotensive effect of delsoline

Delsoline(DS) is a C19-diterpenoid alkaloid isolated from the roots of Aconitum finetianum Hand-Mazz. With ip DS 1.25, 2.5 in anesthetized dogs and 10 mg/kg in rats, the arterial blood pressure (BP) decreased rapidly by 30%,47% and 20%,respectively.Afterwards, the reduced BP gradually returned to the control levels. In conscious rats hypertension induced by ligation of left renal artery, DS 75 mg/kg (qd* 6 d) ip resulted in a marked fall of systolic BP accompanied by a slow heart rate and an early enhanced respiration amplitude. Experiments on the superior cervical, celiac and intracardiac vagal ganglia of dogs revealed that DS had a ganglioblocking effect.DS 6-8 mg injected into anterior tibial artery of rabbits exhibited a curare-like effect on the anterior tibial muscles. DS produced a negative inotropic action on isolated heart of frogs and rabbits or intact heart of dogs. When blood from right femoral artery was pumped at a constant speed into left femoral artery in dog, vascular resistance in left hind-limb and carotid BP were conspicuously reduced by iv DS 2.5 mg/kg. When DS 0.25 mg/kg was injected into the femoral artery, the vascular resistance increased slightly but the carotid BP did not change. DS 2.5 mg/kg inhibited the pressor reflex initiated by bilateral carotid occlusion, but did not antagonize or reverse the pressor reponse resulted from iv epinephrine 10 mcirog in dogs. These results suggest that hypotensive effect of DS is mainly attributable to its ganglionic blocking. Its negative cardiac inotropic effects is involved in the hypotensive action. Since the hypotension can be significantly attenuated by diphenhydramine,histamine release may also playa role in the hypotensive effect.The acute LD50 of DS in mice were iv 117 mg/kg and ip 329 mg/kg.