Calcitonin gene-related peptide (CGRP) is a sensory nerve-derived neuropeptide and the most potent microvascular vasodilator known to date. Suggested previously to be protective in a range of models of hypertension1, the aim of this study was to learn the influence of CGRP on vascular mechanisms in an angiotensin-II (Ang II) model of hypertension. Matched C57BL/6 wildtype (WT) and selective αCGRP knockout (KO) mice were anaesthetised and osmotic minipumps with Ang II (1.1 mg/kg/day for 14 days or 0.9mg/kg/day for 21 days) or vehicle (saline) were implanted as described previously2. Blood pressure was recorded by tail-cuff plethysmography until days 14/28 when the experiment was terminated. Vascular hypertrophy was assessed by histology and mRNA expression by RT-qPCR. Data were analysed using ANOVA plus Bonferroni’s post test. CGRP deletion did not affect baseline blood pressure regulation under normotensive conditions. Systolic pressure significantly increased after 14 days Ang II in WT (129±3.84) and αCGRP KOs (140±7.23, p<0.001), this being significantly enhanced in the αCGRP KOs (p<0.001). This exacerbated hypertensive response was still apparent at day 28 (204±9.8, p<0.01). αCGRP mRNA expression was upregulated in the aorta and mesentery of hypertensive WTs at both 14 (p<0.01) and 28 (p<0.001) days, indicating the potential for αCGRP to influence in a chronic, in addition to acute manner. Vascular inflammation/remodelling was apparent in hypertensive subjects, characterised by increased collagen expression. This remodelling was exacerbated in Ang II-treated αCGRP KOs at both time-points (p<0.001). This study provides evidence that i) CGRP is upregulated at the vascular level in hypertension and ii) deletion of CGRP is associated with enhanced Ang II-induced hypertension and vascular injury. This suggests a sustained protective role for CGRP in this model.