Louise Juhl

Publications (2)5.03 Total impact

• Article: Effect of two novel CGRP-binding compounds in a closed cranial window rat model.

  Louise Juhl, Lars Edvinsson, Jes Olesen, Inger Jansen-Olesen
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  ABSTRACT: We investigated the in vivo effects of two novel calcitonin gene-related peptide (CGRP) binding molecules in the genuine closed cranial window model in the rat. The RNA-Spiegelmer (NOX-C89) and the monoclonal CGRP antibody are CGRP scavengers and might be used as an alternative to CGRP-receptor antagonists in the treatment of migraine. Rats were anaesthetized and a closed cranial window established. Changes in dural and pial artery diameter and mean arterial blood pressure were measured simultaneously. Infusion of the RNA-Spiegelmer or the CGRP antibody alone had no effect on the arteries or the mean arterial blood pressure. We then used a bolus of 0.3 microg/kg CGRP (n=6) or electrical stimulation (25 V, 5 Hz, 1 ms pulse width and of 10 s of duration) (n=6) to induce dilatation of dural and pial arteries (mediated via CGRP-receptors). Pre-treatment with the RNA-Spiegelmer inhibited CGRP-induced vasodilatation of the dural artery (from 38+/-17% to 7+/-3%) and the pial artery (from 14+/-1% to 3+/-2%) (P<0.05). The RNA-Spiegelmer, however, did not significantly inhibit dilatation induced by electrical stimulation (P>0.05). The CGRP antibody caused a significant reduction of the dural artery diameter caused by intravenous CGRP-infusion (from 23+/-5% to 12+/-3%) (P<0.05), but did not inhibit dilatation caused by electrical stimulation (P>0.05). In conclusion, the CGRP scavengers effectively inhibited the effect of circulating CGRP but do not modify the effect of electrical stimulation and the consequent liberation of CGRP from perivascular sensory nerve fibres.
  European Journal of Pharmacology 08/2007; 567(1-2):117-24. · 2.52 Impact Factor
• Article: The in vivo effect of adrenomedullin on rat dural and pial arteries.

  Louise Juhl, Kenneth Ahrend Petersen, Erik Hviid Larsen, Inger Jansen-Olesen, Jes Olesen
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  ABSTRACT: 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.
  European Journal of Pharmacology 06/2006; 538(1-3):101-7. · 2.52 Impact Factor