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 micrograms/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 micrograms/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.
Taylor
B K
BK
Department of Pharmacology, University of California, San Diego, La Jolla.
Holloway
D
D
Printz
M P
MP
D000818:Animals; D001919:Bradycardia / Q000209:etiology*; D018680:Cholinergic Antagonists; D006426:Hemicholinium 3 / Q000494:pharmacology; D006973:Hypertension / Q000209:etiology*; D010830:Physostigmine / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011950:Receptors, Cholinergic / Q000502:physiology*; D013216:Reflex, Startle; D012601:Scopolamine / Q000494:pharmacology; D013045:Species Specificity
D018680:Cholinergic Antagonists; D011950:Receptors, Cholinergic; D006426:Hemicholinium 3; D010830:Physostigmine; D012601:Scopolamine