A clinical study on the role of the renin-angiotensin-aldosterone system and catecholamines in chronic congestive heart failure.

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Abstract
To evaluate the roles of the renin-angiotensin-aldosterone system and of catecholamines in 117 normotensive patients with chronic congestive heart failure (CHF), the relationships between plasma concentrations, hepatic extraction of these humoral factors and hemodynamic parameters were studied. In 6 patients with moderate to severe CHF, the acute effect of oral administration of angiotensin I-converting enzyme inhibitor, SQ 14225 (captopril), on mean arterial pressure (MAP), peripheral venous pressure (VP) and these humoral factors were investigated. In patients with CHF of class III-IV (according to NYHA [New York Heart Association] classification), the urinary norepinephrine (U-NE) excretion increased. Plasma norepinephrine (P-NE) levels increased in proportion to the severity of CHF (P < 0.001) and had a positive correlation with systemic vascular resistance (SVR) (P < 0.01), VP (P < 0.05), pulmonary artery wedge pressure (PWP) (P < 0.01) and plasma renin activity (PRA) (P < 0.01). P-NE correlated negatively with the cardiac index (P < 0.02). Hepatic extraction of norepinephrine (EX-NE) was reduced in patients with elevated right atrial pressure (RAP) (P < 0.05) and negatively correlated with VP (P < 0.05). In patients with elevated P-NE, U-NE increased significantly (P < 0.01), despite their decreased renal clearance of norepinephrine (CNE) (P < 0.02). There was no significant difference in EX-NE between these patients and patients with normal P-NE. PRA was higher in class III-IV patients than in class I-II patients in the prediuretic period (P < 0.01). PA showed a significant positive correlation with PRA (P < 0.001). Hepatic extraction of aldosterone (EX-A) was reduced in patients with elevated RAP (P < 0.05) and was negatively correlated with VP (P < 0.05). Following captopril administration, PRA increased consistently and PA decreased. MAP fell, especially in 2 patients with mitral stenosis. The heart rate tended to decrease. VP also fell with symptomatic improvement. The decline in VP was correlated with the decrease in P-NE (P < 0.01). Apparently, the sympathetic nervous system contributes to the elevation of SVR an PWP even before Franks'' heart failure develops. The rise of P-NE seems to be due to increased norepinephrine release from sympathetic nerve beds, whereas a decrease in hepatic extraction and renal clearance probably has only a minor effect. The renin-angiotensin system also seems to contribute to elevation of SVR, maintaining effective arterial pressure in patients with severe heart failure. PRA may be regulated partly by enhanced sympathetic activity, and the renin-angiotensin system seems to be a main determinant of PA in CHF.