3.9 Article

Calcitonin gene-related peptide (CGRP) in autonomic cardiovascular regulation and vascular structure

Journal

JOURNAL OF THE AMERICAN SOCIETY OF HYPERTENSION
Volume 8, Issue 5, Pages 286-296

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.jash.2014.03.001

Keywords

Baroreflex sensitivity; catecholamines; sympathetic activities; vagal tone

Funding

  1. National Center for Advancing Translational Sciences of the National Institute of Health (NTH) under Award [UL1 TR000445]
  2. Vanderbilt International Students and Scholars Program
  3. American Heart Association predoctoral fellowship [13PRE14480008]
  4. [P01HL056693]
  5. [U54 NS065736]

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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. Barorefiex 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. (C) 2014 American Society of Hypertension. All rights reserved.

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