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 hypertensive rats, we evaluated the contribution of central cholinergic mechanisms to the pathology of hypertension. In normotensive Wistar-Kyoto (WKY) rats, transient airpuff stimuli elicit a complex startle reaction consisting of several behavioral and autonomic components. These include jumping (motor response), an increase in blood pressure (pressor response), an early-trial decrease in heart rate (bradycardia) and a later-trial increase in heart rate (tachycardia). Intracerebroventricular (i.c.v.) administration of cholinergic compounds to WKY rats primarily altered the bradycardia component. Thus, depletion of brain acetylcholine with hemicholinium-3 (5 μg/kg i.c.v.) abolished bradycardia responses without significantly affecting the motor response, tachycardia or pretest cardiovascular base-line parameters. Furthermore, enhancement of brain acetylcholine with acetylcholinesterase inhibition (physostigmine, 50 μg/kg i.c.v.) enhanced bradycardia in WKY rats. The nonspecific muscarinic antagonist scopolamine and the M₁ muscarinic receptor antagonist pirenzepine, but neither the M₂ muscarinic antagonist methoctramine nor the nicotinic antagonist hexamethonium, attenuated bradycardia. We conclude that a central M₁ muscarinic receptor participates in the control of startle- associated bradycardia in the WKY rat. The spontaneously hypertensive rat does not normally exhibit startle-associated bradycardia. Because i.c.v. physostigmine revealed early-trial bradycardia in this strain, we conclude that a selective central cholinergic deficit contributes to a suppression of startle-associated bradycardia in the spontaneously hypertensive rats.