Role of nitric oxide in mediating in vivo vascular responses to calcitonin gene-related peptide in essential and peripheral circulations in the fetus

• Published in: Circulation (New York, N.Y.) Vol. 112; no. 16; pp. 2510 - 2516
• Main Authors: THAKOR, A. S, GIUSSANI, D. A
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 18.10.2005
• Subjects: Animals; Biological and medical sciences; Blood and lymphatic vessels; Blood Flow Velocity - drug effects; Blood Flow Velocity - physiology; Calcitonin Gene-Related Peptide - pharmacology; Cardiology. Vascular system; Coronary heart disease; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Femoral Artery - drug effects; Femoral Artery - embryology; Femoral Artery - physiology; Fetus; General and cellular metabolism. Vitamins; Heart; Medical sciences; Nitric Oxide - physiology; Pharmacology. Drug treatments; Regional Blood Flow - drug effects; Sheep; Umbilical Arteries - drug effects; Umbilical Arteries - physiology; Vasodilation - drug effects; Vasomotricity; Nitric oxide; Cardiovascular disease; Fetus; calcitonin gene-related peptide; Calcitonin gene related peptide; Hemodynamics; Neuropeptide; Vasodilation
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.105.562546

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. 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-microg 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. 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.