Cardiovascular responses to intra-hippocampal dynorphin A-(1-8) in spontaneously hypertensive rats.
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)
Wang
J Q
JQ
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858-4353.
Ingenito
A J
AJ
D000375:Aging / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006624:Hippocampus / Q000033:anatomy & histology / Q000502:physiology*; D008297:Male; D008845:Microinjections; D008969:Molecular Sequence Data; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D010446:Peptide Fragments; C051844:norbinaltorphimine; D009271:Naltrexone; D004399:Dynorphins; C026770:dynorphin (1-8)