Circulating adrenomedullin in cirrhosis: relationship to hyperdynamic circulation

Abstract

Background/Aims: Peripheral arterial vasodilation may be the key factor in the sodium and water retention of cirrhosis. The mechanism responsible for this vasodilation remains to be fully elucidated. Adrenomedullin is a novel peptide, highly expressed in cardiovascular tissues, with potent and long-lasting vasodilating activity. Methods: The possible implication of adrenomedullin in the hemodynamic changes of cirrhosis has been investigated. We measured the plasma concentration of adrenomedullin in 20 cirrhotic patients and 11 healthy subjects. In addition, systemic, portal and renal hemodynamics, hormonal factors and renal function parameters were evaluated in the same patients. Results: Circulating adrenomedullin was significantly higher in the group of patients with cirrhosis (72.1; 46-100 vs 21.6; 11-34 fmol/dl, respectively; p∞0.02) and was directly correlated with the Pugh score (r:

Adrenomedullin gene delivery attenuates myocardial infarction and apoptosis after ischemia and reperfusion

“…AM is a potent vasodilator as intravenous administration of the AM peptide produced a hypotensive effect along with a marked reduction of total peripheral resistance in animals and humans (7,19). In addition to influencing the contractile state of blood vessels, AM also inhibits protein and DNA synthesis in cultured cardiac myocytes and fibroblasts, which is mediated via a cAMPdependent pathway (16).…”

Adrenomedullin in cirrhotic and non-cirrhotic portal hypertension

“…Arterial vasodilatation and activation of several vasoactive and neurohumoral systems may play a key role in pathogenesis of sodium and water retention and ascites formation in cirrhosis [1,2] . These changes have been attributed to increased production of vasodilator substances [2,3] . Adrenomedullin (ADM) and nitric oxide (NO) are considered as essential mediators of hyperdynamic state.…”

“…Adrenomedullin (ADM) and nitric oxide (NO) are considered as essential mediators of hyperdynamic state. NO, a potent vasodilator substance synthesized from L-arginin by NO synthase, is increased in cirrhotic patients and experimental models of cirrhosis [3,4] . Specific NO inhibitors have been shown to counteract vasodilatation and hyperdynamic circulation in these groups [4,5] .…”

“…Specific NO inhibitors have been shown to counteract vasodilatation and hyperdynamic circulation in these groups [4,5] . In addition, circulating levels of potent vasodilating peptides (substance P, CGRP), pulsatile blood flow, and shear stress could contribute to the up regulation of endothelial NO-synthase (e-NOS) [3,6] . ADM is a potent endogenous vasorelaxing factor that was originally isolated from the extracts of human pheochromocytoma [7] .…”

“…ADM is a potent endogenous vasorelaxing factor that was originally isolated from the extracts of human pheochromocytoma [7] . ADM is expressed in adrenal gland, lungs, kidneys, smooth muscle vascular endothelial cells, and splanchnic organs [3,8] . ADM level is increased after stimulation with bacterial endotoxin and cytokines [9] .…”