Kindled seizures activate both branches of the autonomic nervous system

Amygdaloid kindled seizures in the rat induce an abrupt elevation of blood pressure accompanied by a significant decrease in heart rate. The autonomic pharmacology of this response was examined in unanesthetized kindled rats. Muscarinic receptor blockade with atropine (1 mg/kg, intravenous (i.v.)) abolished the seizure-induced bradycardia. The seizure-induced hypertension was unaffected by beta-adrenergic blockade with timolol (1 mg/kg, i.v.), but was reduced by phentolamine (5 mg/kg, subcutaneous (s.c.)), an alpha-adrenergic receptor antagonist. A chemical sympathectomy was induced with 6-hydroxydopamine (100 mg/kg, i.v.), an agent that does not cross the blood-brain barrier. This eliminated the pressor response but did not completely block the seizure-induced bradycardia. The effectiveness of 6-hydroxydopamine was tested with tyramine (0.5 mg/kg, i.v.) an agent that releases endogenous catecholamines. These results indicate amygdaloid kindled seizures activate both branches of the autonomic nervous system. The bradycardia was mediated by the parasympathetic system; the pressor response was caused by an increase in peripheral resistance due to alpha-adrenergic receptor activation. More important, these findings show that kindling is a useful seizure model for future studies on the effect of seizures on cardiovascular function and possible mechanisms of seizure-related sudden unexplained death.