Targeted disruption of adrenomedullin and αCGRP genes reveals their distinct biological roles

Adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) share common structural characteristics and receptors and belong to the same peptide family. Both peptides show a diverse set of biological effects including vasodilation. Recent establishment of gene-knockout mice has revealed the physiological importance of these two peptides. AM-/- mice demonstrated defective vascular formation during embryogenesis and did not survive beyond midgestation. AM+/- heterozygous mice showed high blood pressure and susceptibility to tissue injury. On the other hand, alphaCGRP-/- mice demonstrated elevated peripheral vascular resistance and high blood pressure caused by increased peripheral sympathetic activity. Thus, AM and CGRP have distinct physiological roles. AM is indispensable for normal embryonic development, regulation of blood pressure and tissue protection against injury, whereas alphaCGRP contributes to the regulation of cardiovascular function through inhibitory modulation of sympathetic nervous activity.