Hypotension induced by intravascular administration of nerve growth factor in the rat.
1. The observation that the area postrema expresses a high level of nerve-growth-factor-receptor immunoreactivity prompted an investigation of the effects of nerve growth factor on autonomic function in the rat. 2. Bolus injection of pharmacological doses of the peptide via the femoral vein led to reproducible, dose-dependent falls in blood pressure. 3. Administration via the vertebral artery, a more direct route to the brainstem, did not appear to lower the threshold dose required to induce hypotension. Furthermore, pretreatment with hexamethonium did not inhibit the hypotensive response to nerve growth factor. 4. Administration of a second dose of nerve growth factor after recovery from the first injection produced little or no fall in blood pressure. Similarly, pretreatment with the mast cell degranulating agent, compound 48/80, rendered the animal refractory to nerve growth factor. 5. The fall in blood pressure induced by nerve growth factor was markedly attenuated by pretreatment with chlorpheniramine. 6. It is concluded that the fall in blood pressure induced by intravenous administration of pharmacological doses of nerve growth factor is mediated by vasoactive substances, particularly histamine, released from mast cells.
Yan
Q
Q
Department of Pharmacology, Washington University School of Medicine, St Louis, Missouri.
Settle
S L
SL
Wilkins
M R
MR
D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects*; D002744:Chlorpheniramine / Q000494:pharmacology; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005268:Femoral Vein; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D051379:Mice; D009414:Nerve Growth Factors / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014711:Vertebral Artery; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D009414:Nerve Growth Factors; D002744:Chlorpheniramine; D003189:p-Methoxy-N-methylphenethylamine