Plasma Norepinephrine, Weak Neurotransmitters, and Renin Activity During Active Tilting in Liver Cirrhosis: Relationship With Cardiovascular Homeostasis and Renal Function

Abstract

Derangements in cardiovascular homeostasis are well–known features of liver failure. To evaluate the role of possible alterations in adrenergic and reninangiotensin systems in this context, tilting–induced changes in plasma norepinephrine, octopamine, β–phenylethanolamine, and plasma renin activity were related to modifications in blood pressure, heart rate, plasma volume, and renal function in 10 healthy controls and 20 patients with liver cirrhosis. After 2 hr of bed rest, the patients had higher norepinephrine (p < 0.05), octopamine, β–phenyl–ethanolamine (p < 0.001), plasma renin activity (0.1 ± p ± 0.05), heart rate (p < 0.05), and lower mean arterial pressure (0.1 ± p ± 0.05). Renal function was characterized by reduced creatinine clearance and filtered sodium (p < 0.001); tubular rejection fraction of sodium and sodium excretion were not significantly reduced. After the change in posture (observation period of 1 hr), tilting–induced tachycardia was abolished in patients who also showed a significant drop in blood pressure after a transient initial increase at 10 min, whereas a steady state was observed in normal subjects. Norepinephrine and plasma renin activity increases were greater and more prolonged in cirrhotics than in controls; octopamine and β–phenylethanolamine did not change in the latter and increased in the former, where they correlated with plasma norepinephrine in basal conditions and after tilting (r ± 0.49). Creatinine clearance, filtered sodium, and tubular rejection fraction of sodium underwent a greater decrease in cirrhotics. Although plasma volume reduction was more evident in cirrhotics, it remained steady after 10 min in both groups. In basal conditions and after tilting (60 min), plasma renin activity inversely correlated with arterial pressure (p < 0.05) and creatinine clearance (p < 0.01) in cirrhotic patients. In conclusion, the adrenergic system, although hyper stimulated, did not achieve an adequate cardiovascular response which could be due, at least in part, to hyperproduction of weak neurotransmitters. The renin–angiotensin system played a compensatory role and its activation appears to be mainly dependent on intrarenal mechanisms.