In the Preliminary Study, we showed that intermedin is a pituitary-derived hypotensive factor signaling through CRLR/RAMP receptor complexes in vessel endothelium. Based on studies of related hormones, adrenomedullin and CGRP, intermedin likely reduces blood pressure by exerting a vasodilator effect on vascular beds. Earlier studies have shown that the neuropeptide αCGRP is predominately produced in the sensory neuron, and serotonin can selectively reduce CGRP secretion by activating the endogenous serotonin (type 1 5-HT1) receptor through the calcium signal pathway. Deletion of the CGRP gene in mutant mice (αCGRP-/-) leads to the elevation of mean arterial pressure, heart rate, peripheral vascular resistance and sympathetic nervous activity as compared to wild-type mice. The other related peptide, adrenomedullin (ADM), initially identified from pheochromocytoma, has been shown to be expressed in various tissues including adrenal medulla, cardiovascular tissues, lung, kidney and placenta. Plasma ADM is elevated in various conditions including cardiovascular and renal disorders and septic shock, and it has been hypothesized that ADM may be involved in the control of circulation and body fluid dynamics in various organs. Studies of mice deficient for ADM showed that ADM is indispensable for cardiovascular development. The homozygous knockout ( Adm－/－) mice exhibited an embryonic lethal phenotype.