Calcitonin gene-related peptide (CGRP) plays an important role in several physiological processes such as vasodilation, cardiovascular homeostasis and transmission of pain. Here we report the generation of a transgenic mouse overexpressing αCGRP and the impact of this on baseline physiological responses. αCGRP transgenic mice displayed significantly increased αCGRP mRNA levels in the kidney, heart and hippocampus. To assess cardiovascular physiology, we measured arterial pressure using a tail cuff system. Heart rate, systolic pressure, mean arterial pressure and diastolic pressure were significantly lower in αCGRP transgenic mice than wild-type mice. To assess pain, a hot plate test was performed and the latency of response was used as an indicator of supraspinal response. In addition, a tail immersion test was performed to assess thermal nociception. A significant increase in latency was observed in the αCGRP transgenic mice when compared with wild-type mice in both tests. These results suggest that αCGRP overexpression causes an increase in thermal reaction and downregulation of the cardiovascular system, presumably due in increased levels of αCGRP.

Atherosclerosis is driven by inflammatory reactions that are shared with the innate immune system. Calcitonin gene related peptide (CGRP) is a potent vasodilator peptide and it is widely distributed in central and peripheral nerve. Recent studies have shown that CGRP can be produced by immune cells such as macrophages following stimulation. However, it is unclear whether CGRP is involved in atherosclerosis development. Here, we investigated whether CGRP has a role in the development of atherosclerosis in apolipoprotein E-deficient (apoE-/-) mice. Newly generated double-knockout apoE-/-/CGRP-/-mice and control apoE-/-mice were fed a high-fat diet from 5 to 10-week-old. ApoE-/-/CGRP-/-mice demonstrated exacerbated atherosclerotic lesion severity with increase total cholesterol level. As a potential mechanism accounting for plaque progression in ApoE-/-/CGRP-/-mice, macrophage migration or adhesion was further investigated and only migration was significantly increased by CGRP depletion. These results suggest that CGRP deletion exacerbated atherosclerosis in apoE-/-mice. Macrophages migration was identified as potential mediators of this effect.