Akinori Nishioka

Effects of captopril on arterial and venous pressure, renal function, and humoral factors in severe chronic congestive heart failure

The effects of captopril in several humoral factors were studied to elucidate the role of the renin‐angiotensin (RA) system in arterial and venous pressures and renal function in patients with severe chronic congestive heart failure. A single oral dose of captopril in 20 subjects reduced mean arterial blood pressure from 77 to 67 mm Hg; this decrease correlated with baseline plasma renin activity (PRA). The increase in PRA and the decrease in plasma aldosterone levels after captopril were much greater in subjects with higher PRA. Plasma norepinephrine (NE) levels decreased, while those of epinephrine did not change. Peripheral venous pressure declined from 107 to 77 mm H2O; this decrease correlated with the change in NE levels. During 7‐day captopril therapy, urine volume and sodium excretion increased (1145 to 1136 ml/day and 76 to 94 mEq/day) in 11 subjects in whom renal function was followed. Renal plasma flow (RPF) rose from 237 to 364 ml/min, while glomerular filtration rate did not change; the filtration fraction decreased from 32% to 23%. Simultaneous infusion of aprotinin in six of the subjects did not affect the captopril‐induced increase in RPF, despite the suppression of plasma bradykinin levels. These results suggest that captopril reduces arterial blood pressure in patients with high PRA through inhibition of the RA system and dilates veins by attenuation of sympathetic nervous activity. Increased RPF and urinary sodium excretion induced by captopril might result from inhibition of the RA system; the kallikrein‐kinin system or bradykinin‐mediated prostaglandins do not appear to play a major role.

Effects of converting-enzyme inhibition on cardiorenal hemodynamics in patients with chronic congestive heart failure

The role of the renin-angiotensin system in cardiorenal function in patients with severe chronic congestive heart failure was investigated. A single oral dose of captopril in 16 patients significantly increased cardiac index and reduced arterial blood pressure and total systemic vascular resistance. These changes were significantly greater in subjects with higher baseline plasma renin activity (PRA). During 7-day captopril therapy, renal plasma flow distinctly increased in 10 patients in whom renal function was followed. The increase found in renal plasma flow was greater in subjects with higher PRA. Yet, the reduction in renal vascular resistance was much greater than that of total systemic vascular resistance, even in patients with lower PRA. Simultaneous infusion of aprotinin in eight of these subjects did not affect the captopril-induced increase in renal plasma flow, despite the suppression of plasma bradykinin levels; these responses were the same in both PRA subgroups. The results suggest that captopril reduces total systemic vascular resistance in patients with chronic congestive heart failure through inhibition of the renin-angiotensin system and that the preferential renal vasodilator effect of captopril might be the sole result of this inhibition, with the kallikrein-kinin system or kinin-mediated prostaglandins not playing a major role.

Effects of Captopril on Cardiorenal Hemodynamics in Patients with Severe Chronic Congestive Heart Failure

The effects of captopril on cardiorenal function were studied in patients with chronic congestive heart failure. A single oral dose of captopril in 16 patients significantly increased cardiac indices and decreased total systemic vascular resistance. These changes were greater in subjects with higher baseline plasma renin activity (PRA). The increase in PRA and decrease in plasma aldosterone were also greater in this group. During 7 days of captopril therapy, renal plasma flow distinctly increased in 10 patients in whom renal function was followed. The increase in renal blood flow was greater in subjects with higher PRA. Simultaneous infusion of aprotinin in eight of these subjects did not affect the captopril-induced increase in renal plasma flow: these responses were the same in both PRA subgroups. The results suggest that captopril reduces total systemic vascular resistance in patients with chronic congestive heart failure through the inhibition of the renin-angiotensin system and the preferential renal vasodilating effect of captopril seems exclusively to be the sole result of this inhibition, with the kallikrein-kinin system or kinin-mediated prostaglandins not playing a major role.