SUMMARY The acute effects of the angiotensin converting-enzyme inhibitor captopril on regional blood flow, renal hemodynamics and sodium excretion were studied in 12 patients with severe congestive heart failure. Converting-enzyme inhibition decreased systemic vascular resistance by 27% and increased cardiac index by 16%. Estimated hepatic blood flow decreased 17%, but renal blood flow increased 60%. The ratio of renal-systemic blood flow increased from 0.10 ± 0.01 to 0.14 i 0.02 (p = 0.031). Although renal plasma flow increased from 202.8 ± 28.8 to 323.7 ± 42.7 mI/min (p = 0.008), the glomerular filtration rate did not change significantly from the mean pretreatment value of 82.1 ± 12.3 mI/min. The filtration fraction decreased from 41.3 ± 3.8% to 33.4 ± 4.5% (p = 0.050), while urinary sodium excretion doubled, from 34.5 ± 9.6 to 68.2 ± 19.6 uEq/min. The plasma renin activity increased from 12.6 ± 5.0 to 29.9 ± 8.4 ng/ml/hr (p = 0.030) as plasma aldosterone concentration decreased from 30.5 ± 6.5 to 11.3 ± 1.2 ng/dl (p = 0.010) and norepinephrine concentrations decreased from 774 ± 105 to 618 ± 85 pg/nl (p = 0.020). We conclude that converting-enzyme inhibition reverses renal vasoconstriction in congestive heart failure and redistributes regional blood flow. The natriuresis may be mediated by one or more of the following: improved renal plasma flow, reduction in filtration fraction, suppression of hyperaldosteronism, and lowering of circulatory catecholamine concentrations.ANGIOTENSIN converting-enzyme inhibitors lower systemic vascular resistance and enhance myocardial function in patients with congestive heart failure,'-3 focusing attention upon the renin-angiotensin system as a cause of excessive vascular impedance. The peripheral vasoconstriction that develops in patients with this disorder occurs unequally in the various regional circulatory beds; renal vasoconstriction is particularly severe.4 The greater impairment of renal blood flow (RBF) than of glomerular filtration rate (GFR) may be a prime stimulus to the retention of sodium and water in heart failure.5' 8 Because angiotensin II promotes renal vasoconstriction and sodium retention,7' 8we sought to determine whether converting-enzyme blockade in patients with advanced congestive heart failure might result in renal vasodilatation and natriuresis. Accordingly, we examined the renal plasma flow (RPF), creatinine clearance, urinary sodium excretion (UNAV) and plasma aldosterone concentrations of patients as they began therapy with the orally administered converting-enzyme inhibitor captopril. In addition, to extend earlier observationsg' 10 and establish whether redistribution of blood flow actually occurs after treatment, we measured the plasma clearance of in- docyanine green (CICG) as an index of splanchnic perfusion.The findings reported here suggest that the reninangiotensin system impairs RBF and diminishes sodium excretion in patients with chronic heart failure, and indicate that therapy with convertingenzyme inhibitors causes redistribution of r...

1 To determine the distribution of flow, the regional haemodynamic response to 100 mg of captopril was determined in 36 patients with refractory cardiac heart failure. Measurements included forearm blood flow by venous occlusion plethysmography (eight patients), splanchnic blood flow by indocyanine green clearance (10 patients), and coronary blood flow by thermodilution (12 patients). 2 Cardiac index significantly rose in one hour (1.9 +/‐ 0.1 to 2.2 +/‐ 0.1 1/m/m2, p less than 0.01) while forearm blood flow rose slightly (2.9 +/‐ 0.8 to 3.2 +/‐ 0.3 ml/100 ml/min). Renal blood flow rose significantly by 30% (344 +/‐ 48 to 533 +/‐ 82 ml/min, p less than 0.02). Despite a fall in rate pressure product (8.8 +/‐ 0.7 to 7.1 +/‐ 0.5 mm Hg bt x 10(3), p less than 0.02), coronary blood flow did not significantly change (160 +/‐ 20 to 133 +/‐ 12 ml/min), indicating an improved supply‐demand relationship. 3 External myocardial efficiency improved (19 +/‐ 3 to 26 +/‐ 6%, p less than 0.05). Coronary blood flow is unaffected and converting‐enzyme inhibitor improves myocardial efficiency. This strategic reduction in vascular impedence distinguishes converting‐ enzyme inhibitors as a unique class of vasodilators in the treatment of coronary heart failure.

Labetalol is a competitive inhibitor of alpha‐ and beta‐adrenergic receptors and has an antihypertensive action. To determine limb haemodynamic effects, we measured calf blood flow and venous capacitance by venous occlusion plethysmography before and after oral labetalol in 10 patients 3‐7 days following coronary bypass surgery. Vascular resistance was calculated as the ratio of mean arterial pressure to arterial flow. The peak effect of labetalol was taken as the point of maximum blood pressure decline, and this interval was selected for evaluation of the limb haemodynamic response. Ninety to 120 min after administration of 100‐200 mg of labetalol the mean blood pressure fell from 88 +/‐ 3 to 79 +/‐ 3 mm Hg; (P less than 0.005). The mean arterial blood flow registered 5.1 +/‐ 1.0 ml 100 ml‐1 limb tissue min‐1 which was not significantly different from the control value of 4.4 +/‐ 0.8 ml 100 ml‐1 limb tissue min‐1. The calculated index of limb vascular resistance was not affected by labetalol administration, averaging 37 +/‐ 12 mm Hg 100‐1 ml limb tissue min‐1 before labetalol and 30 +/‐ 11 mm Hg ml‐1 100 ml limb tissue min‐1 at the time of peak hypotensive effect. There was a slight but statistically significant increment in limb venous volume to 1.9 +/‐ 0.3 from 1.5 +/‐ 0.3 ml 100 ml‐1 limb tissue (P less than 0.025). Placebo administration produced no consistent changes in blood pressure, arterial blood flow, vascular resistance or venous capacitance.(ABSTRACT TRUNCATED AT 250 WORDS)

1 In a placebo-controlled, double-blind, randomized, parallel group study one hundred and one patients with supine diastolic blood pressure -100 mm Hg phase V, despite treatment with atenolol 100 mg plus chlorthalidone 25 mg once daily also received either felodipine 5-20 mg twice daily or hydralazine 25-100 mg twice daily for 6 weeks. 2 Felodipine achieved a lower supine blood pressure (mean + s.d. 177/108 + 29/8-138/82 ± 19/8 mm Hg) than hydralazine (174/109 + 25/8-149/92 + 26/11 mm Hg), (P < 0.05/P < 0.001). Felodipine also lowered supine diastolic blood pressure to < 90 mm Hg more often than hydralazine (42 vs 22 patients, P < 0.001). 3 The incidence of unwanted effects was similar in both groups. The felodipine treated patients experienced more ankle swelling and flushing than those in the hydralazine group who experienced more headache and minor gastro-intestinal upset.