Effect of dynorphin microinjection in the paraventricular nucleus on the hemodynamic response to hemorrhage in the rat.
We studied the effect of dynorphin A-(1-13), dynorphin A-(1-17), des-tyr dynorphin A-(2-17) (inactive at opioid receptor) or normal saline (NS) microinjected into the paraventricular nucleus (PVN) (n = 9/treatment) on mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV), and left ventricular stroke work (LVSW) during fixed-volume hemorrhage in conscious rats. Microinjection of dynorphin A-(1-13) (6 nmol) into PVN at 15 min following the termination of fixed volume hemorrhage (8 ml/300 g) significantly decreased MAP from 50 min to 2 hr postinjection (P < 0.05 compared to animals receiving NS), while dynorphin A-(1-17) (6 nmol) significantly decreased MAP from 30 min up to 2 hr postinjection (P < 0.05). Microinjection of des-tyr dynorphin A-(2-17) (6 nmol) into the PVN did not significantly affect MAP following hemorrhage. Recovery of MAP in the dynorphin A-(1-13) and dynorphin A-(1-17) groups following hemorrhage was found to be significantly attenuated compared to the NS group (P < 0.05 and P < 0.01, respectively). Dynorphin A-(1-13) increased heart rate at 20 min and decreased stroke volume at 60 min after microinjection directly into the PVN following hemorrhage when compared with the NS group (P < 0.05). Both dynorphin A-(1-13) and dynorphin A-(1-17) significantly decreased LVSW after PVN injection following hemorrhage compared to NS group (both P < 0.05). No significant effects were observed on CO following microinjection of active or inactive opioid peptides into the PVN following hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)
Fan
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Division of Neurosurgery, University of Pennsylvania, Philadelphia 19104-6316.
McIntosh
T K
TK
D000818:Animals; D002319:Cardiovascular System / Q000503:physiopathology; D004399:Dynorphins / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D006470:Hemorrhage / Q000503:physiopathology*; D008297:Male; D008845:Microinjections; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
D010446:Peptide Fragments; C026843:dynorphin (1-13); D004399:Dynorphins; C082245:dynorphin (2-17)