Enhanced Urinary Excretion of cGMP in Liver Cirrhosis (Relationship to Hemodynamic Changes, Neurohormonal Activation, and Urinary Sodium Excretion)

Cyclic guanosine monophosphate (cGMP) has beenproposed to mediate peripheral arterial vasodilation inliver cirrhosis. Nitric oxide and natriuretic peptidesare the main signals for cGMP generation. Variation in urinary cGMP excretion parallels changes inplasma cGMP levels. Our aim was to determine urinaryexcretion of cGMP (UcGMPV) and to investigate itsrelationship to systemic hemodynamics, neurohumoral activity and renal sodium excretion incirrhosis. Urinary excretion of cGMP was measured in 19healthy subjects and 20 patients with alcoholiccirrhosis. Systemic hemodynamic parameters, blood volume(BV), plasma atrial natriuretic factor (ANF), and theendothelium-dependent vasodilator substance P (SP) weredetermined in all patients and in five healthy subjects.Urinary cGMPV was higher in the group of patients (736 pg/min; 50 -3229 pg/min) than incontrols (126 pg/min; 0-1657 pg/min) (P < 0.01). Inaddition, UcGMPV inversely correlated with the systemicvascular resistance and directly with cardiac output, blood volume, SP, ANF, and Pugh's score. By Coxregression analysis, only systemic vascular resistanceremained inversely associated with UcGMPV. Inconclusion, urinary cGMP excretion is increased incirrhosis. It is suggested that increased cGMP generationmay be related to the hyperkinetic circulation in humancirrhosis.