The in vivo effect of adrenomedullin on rat dural and pial arteries.
Adrenomedullin is related to the calcitonin gene-related peptide (CGRP) family and is present in cerebral blood vessels. It may be involved in migraine mechanisms. We measured the change in dural and pial artery diameter, mean arterial blood pressure and local cerebral blood flow flux (LCBF(Flux)) after intravenous (i.v.) infusion of adrenomedullin. The study was performed in the presence or absence of the CGRP1 (calcitonin-receptor-like-receptor (CALCRL)/receptor activity-modifying protein-1 (RAMP1)) receptor antagonists BIBN4096BS, CGRP-(8-37) and the adrenomedullin receptor antagonist adrenomedullin-(22-52). I.v. infusion of 15 mug kg(-1) adrenomedullin (n=8) induced dilatation of dural (32+/-7.5%) and pial (18+/-5.5%) arteries, a reduction in mean arterial blood pressure (19+/-3%) and an increase in LCBF(Flux) (16+/-8.4%). The duration of the responses was 25 min for the dural artery, while the response of the pial artery lasted for 15 min. The CGRP1-receptor antagonists BIBN4096BS and CGRP-(8-37) and the adrenomedullin receptor antagonist adrenomedullin-(22-52) significantly inhibited the effect of adrenomedullin (n=7, P<0.05 for both arteries) on dural and pial artery diameter and mean arterial blood pressure. No significant inhibition of LCBF(Flux) was found. The antagonist alone had no effect on mean arterial blood pressure or LCBF(Flux). In conclusion, we suggest that adrenomedullin in the rat cranial circulation dilates dural and pial arteries, reduces mean arterial blood pressure and increases LCBF(Flux), probably via a CGRP1-receptor.
Juhl
Louise
L
Department of Neurology, Glostrup Hospital, University of Copenhagen, DK-2600 Glostrup, Denmark. loujuh01@glostruphosp.kbhamt.dk
Petersen
Kenneth Ahrend
KA
Larsen
Erik Hviid
EH
Jansen-Olesen
Inger
I
Olesen
Jes
J
D053607:Adrenomedullin; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004388:Dura Mater / Q000098:blood supply; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D010841:Pia Mater / Q000098:blood supply; D010879:Piperazines / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
D010446:Peptide Fragments; D010455:Peptides; D010879:Piperazines; D011799:Quinazolines; D014665:Vasodilator Agents; C104782:adrenomedullin (22-52); C058636:calcitonin gene-related peptide (8-37); D053607:Adrenomedullin; D015740:Calcitonin Gene-Related Peptide; C406305:olcegepant