The renin-angiotensin-aldosterone system and catecholamines in chronic congestive heart failure. Effect of angiotensin I converting enzyme inhibitor SQ 14225 (Captopril).

Abstract

In order to elucidate the role of the renin-angiotensin-aldosterone system and catecholamines in the pathophysiology of chronic congestive heart failure (CHF), a study was made of the relationship between these humoral factors and the hemodynamic parameters. In 36 patients with various degrees of CHF, urinary norepinephrine (U-NE) was significantly increased in Class III-IV (NYHA) patients with a positive correlation to total systemic vascular resistance (SVR) (p < 0.05) as well as to peripheral venous pressure (VP) (p < 0.05). Plasma renin activity (PRA) was increased in Class IV patients and tended to be positively correlated with SVR. Plasma aldosterone levels (PA) correlated well with PRA (p < 0.01). In six Class III-IV patients, the acute effect of oral angiotensin I converting enzyme inhibitor SQ 14225 (captopril) on mean arterial pressure (MAP), VP, PRA, PA and plasma catecholamines was examined. PRA was consistently increased (306%) and PA decreased (37%) following captopril administration, indicating that captopril effectively inhibited angiotensin 11 formation. MAP fell (17%), especially in two patients with mitral stenosis. The heart rate tended to decrease (7%). VP also fell (27%) with symptomatic improvement. The decline in VP correlated with the decrease in plasma norepinephrine concentrations (P-NE) (p < 0.01). In patients with mitral stenosis, urine volume decreased as blood pressure fell. In two patients with CHF refractory to conventional treatment, captopril induced increased urinary sodium excretion and body weight reduction despite only a slight fall in MAP and was useful as chronic unloading therapy. These results suggest that norepinephrine plays a role in elevating SVR as well as VP, and the renin-angiotensin system also appears to contribute to the rise in SVR in CHF when the circulatory impairment is more severe. Captopril seems to dilate arterioles by reducing angiotensin 11 levels and also to reduce VP by decreasing P-NE. It is a useful therapeutic measure in selected patients with severe CHF.