Effects of dynorphin A(1-13) and of fragments of beta-endorphin on blood pressure and heart rate of anesthetized rats.
The effect on blood pressure and heart rate of central administration of dynorphin A(1-13) and of beta-, gamma-, and alpha-endorphin related peptides was studied in urethane-anesthetized rats. Intracerebroventricular (i.c.v., 0.1-10 micrograms) administration of beta-endorphin resulted in a dose-dependent, naltrexone-reversible hypotension and bradycardia. N-terminally modified fragments of beta-endorphin did not reduce blood pressure and heart rate. On the other hand, a dose of 10 micrograms of beta-endorphin(1-27), which lacks the four C-terminal amino acid residues of beta-endorphin, induced a fall in blood pressure and had a biphasic effect on heart rate. These responses, however, were resistant to pretreatment with naltrexone. None of the fragments of beta-endorphin smaller than beta-endorphin(1-27) affected blood pressure when administered i.c.v. in a dose of 10 micrograms. A small transient bradycardia was observed after i.c.v. administration of 10 micrograms of beta-endorphin(1-26), alpha, and gamma-endorphin. The naltrexone-reversible bradycardic response of alpha- and gamma-endorphin was not present in des-tyrosine- and des-enkephalin-alpha- and gamma-endorphin and also not in alpha-endorphin(10-16) and gamma-endorphin(10-17). Upon i.c.v. administration (0.1-50 micrograms) a dose-dependent, naltrexone-reversible decrease in blood pressure and heart rate was induced by dynorphin A(1-13). The present data indicate a hypotensive influence of beta-endorphin, beta-endorphin(1-27), and dynorphin A(1-13), whereas other fragments of beta-endorphin had little or no effect on the cardiovascular parameters investigated.
Rudolf Magnus Institute for Pharmacology, Medical Faculty, State University of Utrecht, The Netherlands.
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PL
van Giersbergen
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H
de Lang
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de Jong
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004399:Dynorphins / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D007276:Injections, Intraventricular; D009271:Naltrexone / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D001615:beta-Endorphin / Q000494:pharmacology*
D009294:Narcotics; D010446:Peptide Fragments; D009271:Naltrexone; D001615:beta-Endorphin; C026843:dynorphin (1-13); D004399:Dynorphins