Vasoactive substances in the circulatory dysfunction of cirrhosis

Patients with cirrhosis and portal hypertension exhibit characteristic haem odynamic changes with a hyperkinetic systemic circulation, abnormal distrib ution of the blood volume, and neurohumoral dysregulation. Moreover, the ci rculating levels or several vasoactive substances may be elevated. Splanchn ic vasodilatation is of pathogenic significance for the low systemic vascul ar resistance and abnormal volume distribution, which are important element s in the development of the concomitant cardiac dysfunction, recently terme d cirrhotic cardiomyopathy. The systolic and diastolic functions are impair ed with direct relation to the degree of liver dysfunction. Significant pat hophysiological mechanisms seem to include a reduced beta -adrenergic recep tor signal transduction, defective cardiac excitation-contraction coupling, and conductance abnormalities. Various vasodilators, such as nitric oxide and calcitonin gene-related peptide, are among candidates in the vasodilata tion and the increased arterial compliance recently described in advanced c irrhosis. Reflex-induced enhanced sympatho-adrenal activity, activation of the renin-angiotensin-aldosterone system, and elevated circulating vasopres sin and endothelin-1 are implicated in the haemodynamic counter-regulation in cirrhosis. Recent research has focused on the assertion that the haemody namic and neurohumoral abnormalities in cirrhosis are part of a general car diovascular dysfunction influencing the course of the disease, with reducti on of organ function and sodium-water retention as the outcome. These aspec ts are relevant to therapy.