Interaction of ouabain and propranolol in the central nervous system. Neurally-mediated effects on the cardiovascular...

The effect of intracerebroventricular (i.c.v.) ouabain alone and after pretreatment with i.c.v. (+/-)-propranolol, (+)-propranolol, UM-272 (a quaternary analogue of propranolol) and lignocaine, on arterial blood pressure (BP), heart rate (HR) and cardiac rhythm was investigated in chloralose anesthetized, vagotomized cats. Ouabain elicited an increase in BP and HR followed by cardiac arrhythmias of ventricular origin. Pretreatment with (+/-)-propranolol, (+)-propranolol or UM-272 attenuated/prevented the cardiovascular effects of ouabain whereas lignocaine did not modify the response appreciably. Since UM-272, which lacks local anesthetic activity and beta-blocking activity also shared the antagonism with (+/-)-and (+)-propranolol, it is deduced that neither beta-blocking nor local anesthetic activity of propranolol could be responsible for this antagonism. This is supported by the fact that lignocaine which has a comparable local anesthetic effect of propranolol failed to modify significantly the cardiovascular response to ouabain. The antagonism appears to be a direct neural depressant effect independent of local anesthetic action. The neural depressant effect may be due to an interference in depolarization process and/or a neurone-blocking effect.