Acute cardiovascular and autonomic effects of WR 2721: a radioprotective compound

WR 2721 is a chemical which has shown much promise as a protective agent in animals exposed to ionizing radiation. Experiments on anesthetized dogs and cats indicate that WR 2721 has little acute cardiovascular action in these animals when given intravenously in doses of 50-200 mg/kg. A total cumulative dose of 600 mg/kg within 2 hr was not lethal and, indeed, was well tolerated. Arterial blood pressure was not markedly lowered in dogs and cats given these doses. In dogs, a slight vasodilation was noted in the femoral vascular bed after intraarterial injection. Mydriasis and watery salivation were observed in all animals. In the dog, WR 2721 (100 mg/kg) produced blockade of the bilateral carotid artery occlusion pressor response, the pressor response to the ganglionic stimulant DMPP, and the bradycardia to vagus nerve stimulation. In the cat, WR 2721 (100 mg/kg) also blocked the contraction of the cat nictitating membrane due to stimulation of the preganglionic fibers of the superior cervical ganglion, but not the contraction seen with postganglionic fiber stimulation. The experiments indicate that WR 2721 is a ganglionic blocking agent. It does not share this property with closely related structural congeners.