PMID- 8138921
OWN - NLM
STAT- MEDLINE
DCOM- 19940425
LR  - 20181130
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 268
IP  - 3
DP  - 1994 Mar
TI  - A unique central cholinergic deficit in the spontaneously hypertensive rat: 
      physostigmine reveals a bradycardia associated with sensory stimulation.
PG  - 1081-90
AB  - 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.
FAU - Taylor, B K
AU  - Taylor BK
AD  - Department of Pharmacology, University of California, San Diego, La Jolla.
FAU - Holloway, D
AU  - Holloway D
FAU - Printz, M P
AU  - Printz MP
LA  - eng
GR  - HL35018/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Cholinergic Antagonists)
RN  - 0 (Receptors, Cholinergic)
RN  - 312-45-8 (Hemicholinium 3)
RN  - 9U1VM840SP (Physostigmine)
RN  - DL48G20X8X (Scopolamine)
SB  - IM
MH  - Animals
MH  - Bradycardia/*etiology
MH  - Cholinergic Antagonists
MH  - Hemicholinium 3/pharmacology
MH  - Hypertension/*etiology
MH  - Physostigmine/*pharmacology
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
MH  - Receptors, Cholinergic/*physiology
MH  - *Reflex, Startle
MH  - Scopolamine/pharmacology
MH  - Species Specificity
EDAT- 1994/03/01 00:00
MHDA- 1994/03/01 00:01
CRDT- 1994/03/01 00:00
PHST- 1994/03/01 00:00 [pubmed]
PHST- 1994/03/01 00:01 [medline]
PHST- 1994/03/01 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1994 Mar;268(3):1081-90.