Vasodilatory Effect of Adrenomedullin in Mouse Aorta

Abstract

Human adrenomedullin (AM) and human calcitonin gene-related peptide (CGRP) produced a concentration-dependent relaxation in mouse aorta, precontracted with noradrenaline. EC(50) values for AM and CGRP were 9.8 +/- 2.4 and 4.2 +/- 0.1 nmol/l, respectively. AM-mediated vasorelaxation was partially (3-fold) shifted by AM(22-52), the C-terminal AM fragment, but not by CGRP(8-37), a selective CGRP1 antagonist. Both AM(22-52) and CGRP(8-37) failed to inhibit CGRP-mediated vasorelaxation of mouse aorta rings. Binding of rat [(125)I]AM to these membranes was specific. Both human AM and AM(22-52) displaced rat [(125)I]AM binding in a concentration-dependent manner with IC(50) values of 12.0 +/- 4 and 19.4 +/- 8 nmol/l, respectively. In contrast, both human CGRP and CGRP(8-37) were weak in displacing [(125)I]AM binding. Very little specific binding was observed with [(125)I]CGRP. In conclusion, the data presented here demonstrate that the mouse aorta displays AM receptors that mediate vasorelaxation.