A UNIQUE CENTRAL CHOLINERGIC DEFICIT IN THE SPONTANEOUSLY HYPERTENSIVE RAT - PHYSOSTIGMINE REVEALS A BRADYCARDIA ASSOCIATED WITH SENSORY STIMULATION

Using a sensory stimulation (startle) paradigm in normotensive and hyp ertensive rats, we evaluated the contribution of central cholinergic m echanisms to the pathology of hypertension. In normotensive Wistar-Kyo to (WKY) rats, transient airpuff stimuli elicit a complex startle reac tion consisting of several behavioral and autonomic components. These include jumping (motor response), an increase in blood pressure (press er response), an early-trial decrease in heart rate (bradycardia) and a later-trial increase in heart rate (tachycardia). Intracerebroventri cular (i.c.v.) administration of cholinergic compounds to WKY rats pri marily altered the bradycardia component. Thus, depletion of brain ace tylcholine with hemicholinium-3 (5 mu g/kg i.c.v.) abolished bradycard ia responses without significantly affecting the motor response, tachy cardia or pretest cardiovascular base-line parameters. Furthermore, en hancement of brain acetylcholine with acetylcholinesterase inhibition (physostigmine, 50 mu g/kg i.c.v.) enhanced bradycardia in WKY rats. T he nonspecific muscarinic antagonist scopolamine and the M(1) muscarin ic receptor antagonist pirenzepine, but neither the M(2) muscarinic an tagonist methoctramine nor the nicotinic antagonist hexamethonium, att enuated bradycardia. We conclude that a central M(1) muscarinic recept or participates in the control of startle-associated bradycardia in th e WKY rat. The spontaneously hypertensive rat does not normally exhibi t startle-associated bradycardia. Because i.c.v. physostigmine reveale d early-trial bradycardia in this strain, we conclude that a selective central cholinergic deficit contributes to a suppression of startle-a ssociated bradycardia in the spontaneously hypertensive rats.