The in vivo effect of adrenomedullin on rat dural and pial arteries.

TY - JOUR

T1 - The in vivo effect of adrenomedullin on rat dural and pial arteries.

AU - Juhl, L.

AU - Petersen, K. A.

AU - Larsen, E. H.

AU - Jansen-Olesen, I.

AU - Olesen, J.

N1 - Keywords: Migraine; Adrenomedullin; Adrenomedullin receptor antagonist; Cerebral blood flow; Middle cerebral artery; Middle meningeal artery

PY - 2006

Y1 - 2006

N2 - 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 (LCBFFlux) 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 µg 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 LCBFFlux (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 LCBFFlux was found. The antagonist alone had no effect on mean arterial blood pressure or LCBFFlux.In conclusion, we suggest that adrenomedullin in the rat cranial circulation dilates dural and pial arteries, reduces mean arterial blood pressure and increases LCBFFlux, probably via a CGRP1-receptor.

AB - 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 (LCBFFlux) 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 µg 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 LCBFFlux (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 LCBFFlux was found. The antagonist alone had no effect on mean arterial blood pressure or LCBFFlux.In conclusion, we suggest that adrenomedullin in the rat cranial circulation dilates dural and pial arteries, reduces mean arterial blood pressure and increases LCBFFlux, probably via a CGRP1-receptor.

U2 - 10.1016/j.ejphar.2006.03.005

DO - 10.1016/j.ejphar.2006.03.005

M3 - Journal article

C2 - 16643888

SN - 0014-2999

VL - 538

SP - 101

EP - 107

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

IS - 1-3

ER -