Document Detail

Cardiovascular responses to intra-hippocampal dynorphin A-(1-8) in spontaneously hypertensive rats.
MedLine Citation:
PMID:  7913047     Owner:  NLM     Status:  MEDLINE    
Previous studies by us established that dynorphin A-(1-8) concentration in the hippocampal formation of spontaneously hypertensive rat (SHR) brain was much less than in the hippocampus of normotensive controls. The connection between low dynorphins and SHR hypertension was unclear. The object of the present study was to determine (1) whether microinjections of dynorphin A-(1-8) into the hippocampus of anesthetized SHR would produce centrally mediated effects on arterial pressure and heart rate and (2) whether these responses would differ qualitatively or quantitatively from those elicited in normotensive Wistar-Kyoto (WKY) or Sprague-Dawley rats. A statistically significant elevation of arterial pressure was observed in SHR at 8, 12 and 16 weeks compared to WKY and Sprague-Dawley controls at similar ages. There were no significant changes in heart rate of SHR compared to WKY and Sprague-Dawley rats. Intra-hippocampal dynorphin A-(1-8) caused a dose-dependent (0.05, 0.5, 5.0 and 50.0 nmol) hypotension and bradycardia in all strains, and ages but the responses were quantitatively larger in SHR than in the normotensive strains. Nor-binaltorphimine, a selective antagonist for kappa-opioid receptor, pretreated into the hippocampus caused a significant blockade of the dynorphin A-(1-8) responses in all strains. The results established that (1) intra-hippocampal dynorphin A-(1-8) lowered the arterial pressure and heart rate by a central mechanism, in all strains, at all ages tested and (2) the responses were quantitatively greater in SHR than in WKY and Sprague-Dawley strains. The responses appear to involve activation of a kappa receptor in the hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)
J Q Wang; A J Ingenito
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  European journal of pharmacology     Volume:  256     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1994 Apr 
Date Detail:
Created Date:  1994-08-10     Completed Date:  1994-08-10     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  57-64     Citation Subset:  IM    
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858-4353.
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MeSH Terms
Aging / physiology
Amino Acid Sequence
Blood Pressure / drug effects
Dose-Response Relationship, Drug
Dynorphins / pharmacology*
Heart Rate / drug effects
Hemodynamics / drug effects*
Hippocampus / anatomy & histology,  physiology*
Molecular Sequence Data
Naltrexone / analogs & derivatives,  pharmacology
Peptide Fragments / pharmacology*
Rats, Inbred SHR
Rats, Inbred WKY
Rats, Sprague-Dawley
Species Specificity
Grant Support
2 SO7 RR05812-12/RR/NCRR NIH HHS
Reg. No./Substance:
0/Peptide Fragments; 105618-26-6/norbinaltorphimine; 16590-41-3/Naltrexone; 74913-18-1/Dynorphins; 75790-53-3/dynorphin (1-8)

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