HEMODYNAMIC AND RENAL EFFECTS OF URODILATIN BOLUS INJECTIONS IN PATIENTS WITH CONGESTIVE-HEART-FAILURE

Urodilatin (ANF(95-126)) is an analogue of the atrial natriuretic factor (ANF(99-126)), which has been isolated from human urine. Recently we have shown in healthy volunteers, that intravenous bolus injections of synthetic urodilatin produce more pronounced reductions of pulmonary arterial pressure than ANF(99-126). To compare haemodynamic and renal effects of synthetic urodilatin with those of ANF(99-126) in congestive heart failure (CHF), 12 patients (66.3 +/- 1.4 years) received either two high dose intravenous bolus injections of 4 mug kg-1 bw Urodilatin (URO) at a 30 min interval (n = 6) or the same doses of ANF(99-126) (n = 6). Prior to i.v. URO, no URO immunoreactivity was found in human plasma (specific RIA, no crossreactivity to ANF). Similar to ANF, the increase in diuresis (1.4 +/- 0.7 to 3.7 +/- 1.6 ml min-1) and natriuresis (169 +/- 114 to 430 +/- 197 mumol min-1) was moderate after URO in CHF. During the 90 min study period, mean plasma cyclic GMP levels increased much more after URO (by 53.4 +/- 15.1 nM) than after ANF (by 13.1 +/- 3.0 nM; P = 0.04). In contrast to ANF, i.v. bolus injections of URO produced sustained haemodynamic effects in CHF lasting up to 90 min: The average (0-90 min) reduction of systemic vascular resistance was more pronounced after URO (-578 +/- 148) than after ANF (-204 +/- 65 dyn*s*cm-5, P = 0.04). Average increase of stroke volume index (URO: 9.5 +/- 1.9; ANF:2.8 +/- 1.4 ml min-1 m-2; P = 0.02) and reduction of pulmonary capillary wedge pressure (URO: -10.8 +/- 2.1; ANF: -3.9 +/- 1.6 mmHg; P = 0.03) were more prominent after URO. These data indicate that urodilatin bolus injections produce sustained beneficial haemodynamic effects in patients with congestive heart failure, which are prolonged and more pronounced than after ANF. The larger increase in plasma cyclic GMP levels in CHF suggests that in the cardiovascular system of heart failure patients, URO may induce a more potent stimulation of guanylate cyclase coupled ANF receptors than ANF(99-126).