Published online before print October 25, 2001, doi: 10.1161/hh2301.100812
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Submitted on March 27, 2001
Revised on October 15, 2001
Accepted on October 15, 2001
Elevated Sympathetic Nervous Activity in Mice Deficient in 
CGRP
From the Department of Cardiovascular Medicine (Y.O., T.S., Y.K., T.I., Y.W., H.M., Y.I., Y.H., R.N.), Department of Urology (H.N.), Department of Cardiothoracic Surgery (Y.S.), Graduate School of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan; Department of Physiology (Y.K., T.K.), School of Medicine, Chiba University, Ihana, Chiba, Japan; The Hospital International Medical Center of Japan (Y.Y.), Tokyo, Japan; and Division of Integrative Cell Biology (H.K.), Department of Embryogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University, Honjo, Kumamoto, Japan.
* To whom correspondence should be addressed. E-mail: kurihara{at}kaiju.medic.kumamoto-u.ac.jp.
-Calcitonin gene-related peptide (CGRP) is a pleiotropic neuropeptide implicated in a variety of physiological processes. To better understand the biological functions of CGRP, we developed an CGRP-null mouse model using a gene targeting approach. Recordings of mean arterial pressure (MAP) and heart rate (HR) showed that basal MAP and HR were significantly higher in both anesthetized and conscious, unrestrained CGRP-null mice than in corresponding wild-type mice. The elevated MAP in CGRP-null mice was shown to be the result of elevated peripheral vascular resistance by -adrenergic blockade with prazosin and by transthoracic echocardiogram, which revealed no significant differences between CGRP-null and wild-type mice in the stroke volume, fractional shortening, and ejection fraction. Moreover, evaluation of autonomic nervous activity by measuring HR after pretreatment of atropine and/or atenolol and by analyzing arterial baroreceptor reflexes showed sympathetic nervous activity to be significantly elevated in CGRP-null mice; elevated levels of urinary catecholamine metabolites and decreased HR variability in mutant mice were also consistent with that finding. These findings suggest that CGRP contributes to the regulation of cardiovascular function through inhibitory modulation of sympathetic nervous activity.
Key words: calcitonin gene-related peptide • gene targeting • blood pressure • autonomic nervous system • hypertension
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