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(Circulation. 2005;112:2510-2516.)
© 2005 American Heart Association, Inc.

Vascular Medicine

Role of Nitric Oxide in Mediating In Vivo Vascular Responses to Calcitonin Gene-Related Peptide in Essential and Peripheral Circulations in the Fetus

A.S. Thakor, MA; D.A. Giussani, PhD

From the Department of Physiology, University of Cambridge, Cambridge, UK.

Correspondence to Dino A. Giussani, PhD, Department of Physiology, University of Cambridge, Cambridge, CB2 3EG, UK. E-mail dag26{at}cam.ac.uk

Received May 15, 2005; revision received July 6, 2005; accepted July 29, 2005.

Background— The role of calcitonin gene-related peptide (CGRP) in cardiovascular regulation is gaining clinical and scientific interest. In the adult, in vivo studies have shown that CGRP-stimulated vasodilation in several vascular beds depends, at least in part, on nitric oxide (NO). However, whether CGRP acts as a vasodilator in the fetus in vivo and whether this effect is mediated via NO have been addressed only minimally. This study tested the hypothesis that CGRP has potent NO-dependent vasodilator actions in essential and peripheral vascular beds in the fetus in late gestation.

Methods and Results— Under anesthesia, 5 fetal sheep at 0.8 gestation were instrumented with vascular catheters and Transonic flow probes around an umbilical artery and a femoral artery. Five days later, fetuses received 2- and 5-µg doses of exogenous CGRP intra-arterially in randomized order. Doses were repeated during NO blockade with the NO clamp. This technique permits blockade of de novo synthesis of NO while compensating for tonic production of the gas, thereby maintaining basal cardiovascular function. CGRP resulted in potent and long-lasting NO-dependent dilation in the umbilical and femoral circulations, hypotension, and a positive cardiac chronotropic effect. During NO blockade, the femoral vasodilator response to CGRP was diminished. In contrast, in the umbilical vascular bed, the dilator response was not only prevented but reversed to vasoconstriction.

Conclusions— CGRP has potent NO-dependent vasodilator actions in fetal essential and peripheral vascular beds. CGRP-induced NO-dependent effects in the umbilical vascular bed may provide an important mechanism in the control and maintenance of umbilical blood flow during pregnancy.

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CLINICAL PERSPECTIVE

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