Presence and function of the calcitonin gene-related peptide receptor on rat pial arteries investigatedin vitroandin vivo.

CALCITONIN; CALCIUM regulating hormones; LABORATORY rats; ARTERIES; MIGRAINE; ADRENOMEDULLIN

Petersen KA, Nilsson E, Olesen J&Edvinsson L. Presence and function of the calcitonin gene-related peptide receptor on rat pial arteries investigatedin vitroandin vivo. Cephalalgia 2005; 25:424–432. London. ISSN 0333-1024Calcitonin gene-related peptide (CGRP) and related peptides may be involved in migraine pathogenesis. To understand their vasomotor role in the cerebral circulation, we performed two studies, a pressurized arteriography study of the middle cerebral artery (MCA) and a genuine closed cranial window (gCCW)in vivostudy. Using the pressurized arteriography model rat MCAs were mounted on micropipettes, pressurized to 85 mmHg and luminally perfused. The diameter responses to luminally and abluminally applied rat-αCGRP, rat-βCGRP, amylin and adrenomedullin were compared with the resting diameter. Only abluminally applied CGRP induced dilation of the cerebral arteries;Emax forαCGRP andβCGRP were 35 ± 0.5% and 10.8 ± 0.2%. These responses were blocked by CGRP8−37. The gCCW model allowed videomicroscopic visualization of the pial vessels in anaesthetized rats. Changes in vessel diameter to intravenously administeredαCGRP andβCGRP were compared with pre-infusion baseline. Intravenous infusion ofαCGRP andβCGRP in the highest dose induced dilation of the cerebral cortical pial arteries/arterioles of 40.3 ± 7.5% and 49.1 ± 8.4%, respectively. However, this was probably secondary to a decrease in blood pressure of 44.8 ± 3.3 mmHg and 49.2 ± 3.3 mmHg. Our results suggest that CGRP receptors are probably functional on the smooth muscle cells and not on the endothelium of rat cerebral arteries. [ABSTRACT FROM AUTHOR]