Abstract
Calcitonin gene-related peptide (CGRP) is reported to play important roles in cardiovascular regulation in human and animal models. In spite of this, its role remains controversial. We aim to clarify this by studying the autonomic cardiovascular function and vascular structure in CGRP knockout (CGRP(-/-)) mice. Blood pressure (BP) and heart rate (HR) were assessed by telemeters. Urine (24-hour) and blood were collected for catecholamines measurements. Baroreflex sensitivity was assessed using phenylephrine and sodium nitroprusside administered in an acute study. Daytime mean arterial pressure (MAP; 12-hour period) was significantly higher in the CGRP(-/-) mice than in the wild type (WT) mice (114.5 vs. 104.5 mm Hg; P = .04). Norepinephrine was elevated in plasma and 24-hour urine in the knockouts (Urine, 956 vs. 618 pg/mL; P = .004; Plasma, 2505 vs. 1168 pg/mL; P = .04). Paradoxically, cardiovagal baroreflex sensitivity was higher in CGRP(-/-) mice (3.2 vs. 1.4 ms/mm Hg; P = .03). To increase insight, we studied aortic stiffness in CGRP(-/-) mice and found it increased compared with age-matched WT mice, as evidenced by the depression of the compliance curve (P < .05). CGRP(-/-) mice have higher BP due to elevated sympathetic signals and abnormalities in blood vessel structure. Moreover, our data also showed that CGRP plays an important role in the regulation of the cardio-vagal tone.