Plasma renin activity (PRA), plasma renin concentration (PRC), angiotensinogen, angiotensin II (AT II) and plasma aldosterone were determined by radioimmunoassay in 77 patients with cirrhosis of the liver [group I: with ascites, untreated (n=23); group II: patients with ascites during treatment (n=32); group III: after removal of fluids, but under further spironolactone therapy (n=10); group IV: untreated subjects without ascites (n=12)]. With the exception of decreased angiotensinogen values in all groups ranging between 39% (group IV) and 73% (group III) no significant changes of the other parameters of the RAAS were found in untreated patients. A highly significant increase of PRA, PRC, AT II and plasma aldosterone was observed in treated cirrhotics with (group II) or without (group III) ascites. In the total series of patients AT II was closely related to PRA, PRC and aldosterone emphasizing aldosterone secretion. Plasma sodium was inversely correlated to PRA, PRC, AT II and aldosterone, but no relationship was detected between these parameters of the RAAS and plasma potassium. Our results indicate that hyperaldosteronism in cirrhosis appears unlikely to be the major determinant of avid renal sodium retention and ascites formation. An increased activity of the RAAS is most often initiated by therapeutic factors and/or markedly altered electrolyte metabolism. Therefore, basal conditions of the patients to be studied must be well defined to exclude any artificially induced stimulation of the RAAS.

The relationship of the renin-angiotensin-aldosterone system to blood pressure and sodium homeostasis and to renal function was investigated serially in 12 patients with fulminant hepatic failure. The plasma concentrations of renin, angiotensin II, and aldosterone were, in most instances, markedly increased. Systolic blood pressure, which was often very low, showed a significant inverse relationship to the plasma renin concentration, suggesting that the marked stimulation of the system is a homeostatic response to hypotension. However, the plasma renin substrate concentration was markedly decreased, and the conversion of angiotensin II to inactive peptides increased, both of which may have severely limited the full 'expression' of the stimulated system. Renin and angiotensin II levels were both related to creatinine clearance, which was often reduced, but it is not clear as to which was cause and which effect. No relationship between the plasma aldosterone concentration and renal sodium excretion could be detected.

No abstract

Arterial and venous plasma concentrations of total immunoreactive angiotensin II (AT II), its bioactive hepta-octapeptide fraction and its inactive hexapeptide were measured in normal subjects (n=16), in patients with acute viral hepatitis (n=12), and in treated (n=16) and untreated (n=17) patients with cirrhosis of the liver and ascites. Independent of normal or increased values of total immunoreactive AT II, the ratio between the hepta-octapeptides and the hexapeptide remained unchanged. This might indicate continuous octapeptide generation and balanced metabolite turnover throughout the systemic circulation. Moreover, a significant arterio-venous peptide gradient was lacking. It has to be concluded that total venous plasma AT II sufficiently reflects both the arterial hormone concentration and its major fraction of hepta-octapeptides in arterial (79%) and venous (76%) blood.