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Increased circulating calcitonin gene-related peptide (CGRP) in cirrhosis
F Bendtsen1, S Schifter, J H Henriksen
1Department of Clinical Physiology and Hepatology, Hvidovre Hospital, Copenhagen, Denmark.
Insights
Elevated calcitonin gene-related peptide (CGRP) levels are found in cirrhosis patients, potentially explaining the hyperdynamic circulatory state. This potent vasodilator
Area of Science:
- Hepatic Pathophysiology
- Neuropeptide Research
- Cardiovascular Physiology
Background:
- The hyperkinetic circulatory state in cirrhosis is poorly understood, with reduced peripheral vascular resistance being a key unresolved issue.
- Calcitonin gene-related peptide (CGRP), a potent vasodilator, has emerged as a potential factor in circulatory regulation.
Purpose of the Study:
- To investigate the role of calcitonin gene-related peptide (CGRP) in the hyperdynamic circulatory state associated with cirrhosis.
- To determine circulating CGRP concentrations in patients with cirrhosis and compare them to control groups.
Main Methods:
- Measurement of immunoreactive CGRP concentrations in plasma from different vascular beds.
- Comparison of CGRP levels in 35 cirrhotic patients, 8 patients with minor disorders, and 232 healthy individuals.
- Analysis of CGRP levels in relation to cirrhosis severity (Child-Turcotte classification).
Main Results:
- Plasma CGRP levels were significantly elevated in cirrhotic patients compared to both minor disorder patients and healthy controls.
- Circulating CGRP concentrations showed a significant positive correlation with the severity of cirrhosis.
- No significant arterio-venous CGRP differences were observed across major organs, suggesting systemic release and degradation.
Conclusions:
- Elevated circulating CGRP may contribute to the hemodynamic abnormalities observed in cirrhosis.
- The findings suggest widespread CGRP release and degradation, rather than decreased degradation, as the cause of increased plasma CGRP in cirrhosis.
Abstract:
The etiology of the hyperkinetic circulatory state in cirrhosis is equivocal and reduced peripheral vascular resistance is a major unsolved problem in hepatic pathophysiology. It is therefore sensible to search for vasodilators. A recently discovered neuropeptide, calcitonin gene-related peptide (CGRP), is a highly potent vasodilator. We determined the circulating concentration of immunoreactive CGRP in different vascular beds in 35 patients with cirrhosis and in eight patients with minor disorders. Plasma CGRP was significantly increased in the cirrhotic patients compared with patients with minor disorders (59 vs. 46 pmol/l, p less than 0.01), as well as with 232 healthy persons (37 pmol/l, p less than 0.0001). Moreover, circulating CGRP increased significantly with the severity of cirrhosis (Child-Turcotte group A, 56; group B, 59; group C, 71 pmol/l; p less than 0.025). No significant arterio-venous net extraction or release of CGRP was found across the hepato-intestinal system, kidney, lung or limb. In conclusion, elevated circulating CGRP may play a role in the haemodynamic derangement of cirrhosis. The lack of organ arterio-venous differences suggests a widespread release and degradation of CGRP in many tissues and gives no evidence of decreased degradation as the cause of increased plasma CGRP in patients with cirrhosis.