Naloxone-like influence of TRH and ACTH-(4-7) on hypothalamic blood flow autoregulation in the rat.
The influence of intracerebroventricularly (ICV) administered thyrotropin-releasing hormone pGlu-His-Pro-NH2 (TRH), pGlu-His-Phe-NH2 (TRH analog, (TRHa)), Met-Glu-His-Phe(ACTH-(4-7)) and His-Phe-Arg-Trp-Gly (ACTH-(6-10)) on autoregulation of cerebral blood flow was studied in anesthetized, ventilated rats. Autoregulatory capacity of the cerebrovascular bed was tested by hypothalamic blood flow (HBF) and total cerebral blood volume (CBV) determinations during consecutive stepwise lowering of the systemic mean arterial pressure to 80, 60 and 40 mmHg, by hemorrhage. None of the peptides caused a change in resting HBF or CBV upon ICV administration (5 micrograms/kg). However, the same dose of TRH, TRHa and ACTH-(4-7) resulted in impairment of autoregulation. ACTH-(6-10) was not effective. Thus, the disturbed autoregulation may be due to the presence of the dipeptide Glu-His which is common to TRH, TRHa and ACTH-(4-7).
Sandor
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P
Rudolf Magnus Institute for Pharmacology, Medical Faculty, University of Utrecht, The Netherlands.
de Jong
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W
de Wied
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D
D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D006470:Hemorrhage / Q000503:physiopathology; D006706:Homeostasis; D007031:Hypothalamus / Q000098:blood supply*; D007276:Injections, Intraventricular; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*
D010446:Peptide Fragments; D009270:Naloxone; C029578:ACTH (4-7); D013973:Thyrotropin-Releasing Hormone; D000324:Adrenocorticotropic Hormone