HYPOTENSIVE MECHANISM OF THE ALKALOID Nn-9 FROM NELUMBO NUCIFERA

Nn-9 was a non-crystalline alkaloid isolated from the embryo of the seeds of the Asiatic lotus, Nelumbo nucifera. In anesthetized cats, iv.injections of 1—2 mg/kg lowered, after a delay of 1/2—1 minute, the blood pressure by about 50% from the original level, lasting 2—3 hours. In dogs, the blood pressure returned to normal in 1/2 hour. This dosage was ineffective in rabbits. Tachyphylaxis developed on repeated administrations. After the cats were pretreated with Diphenhydramine or Promethazine, the hypotensive effect of Nn-9 was remarkably diminished. Pretreatment with Nn-9 also lessened the hypotensive action of histamine. When the cats were given 2 mg/kg of Nn-9 intravenously, the hypotension was accompanied by a reduction of cerebral vascular resistance. Intra-arterial injections yielded an increase of both cerebral and femoral blood flows, associated with a diminution of the vascular resistance. In spinal cats, i.v. injection of 2 mg/kg produced a significant drop of blood pressure. The pressor responses elicited by i.v. adrenalin, noradrenalin, pituitrin, or by spinal compression below C-7 were all inhibited for 1/2—1 hour. The retraction of nictitating membrane by preganglionic faradization was also inhibited. But it had no apparent influence on parasympathetic ganglion and M-cholinergic reactive system. Intracarotid injections produced a hypotension, together with a decrease of the carotid occlusion reflex pressor response. In conclusion, Nn-9 seems to act primarily through histamine release. Secondarily, a nervous factor is also involved.