Mechanisms involved in the response to prolonged infusion of atrial natriuretic factor in patients with chronic heart failure.

Abstract

We examined the mechanisms involved in the cardiovascular and renal response to prolonged infusion of atrial natriuretic factor (ANF) in patients with chronic heart failure. ANF infusion was titrated to produce a 30% decrease in pulmonary capillary wedge pressure or a 20% increase in cardiac output, and this dose (average, 75 +/- 4 ng/kg/min) was then administered for 20 hours. The short-term response to ANF included significant reductions in central filling pressures, increases in cardiac output, modest increases in diuresis and glomerular filtration rates, significant reduction in plasma aldosterone levels, and a 3.6-fold increase in plasma cyclic GMP levels. During prolonged infusion, plasma cGMP levels and cardiac output gradually returned to baseline. Similarly, the initially increased diuretic effects were completely abolished during prolonged ANF infusion, although plasma alpha-hANF levels remained consistently elevated above baseline values (control, 198 +/- 38; titration, 2,760 +/- 596; 20 hours, 3,499 +/- 659 pg/ml). Four hours after beginning the ANF infusion, marked increases in hematocrit levels were noted (42.5 +/- 1.0% versus 45.3 +/- 1.4%, control and infusion, respectively, p less than 0.05); during this time, no change in total plasma protein concentration occurred, indicating extravascular shift of fluid and plasma proteins. No evidence was noted for activation of vasoconstrictor hormones during prolonged ANF infusion, although mean arterial pressure was significantly reduced throughout the infusion period. Plasma pro-ANF (31-67) levels, determined as a marker for endogenous ANF secretion, were significantly suppressed as were the reductions of central filling pressures. After ANF discontinuation, heart rate and pulmonary capillary wedge pressure increased significantly above baseline values without evidence for sympathetic stimulation. We conclude that 1) prolonged infusion of ANF causes only transient increases in plasma cGMP levels but a sustained reduction of the cardiac release of ANF and that 2) the beneficial hemodynamic effects of ANF, that is, unloading of the ventricles, may be associated with or, in part, may be secondary to a shift of plasma constituents into the extravascular space. The latter may limit the therapeutic potential of ANF for long-term treatment.

Placebo‐controlled comparison of candoxatril, an orally active neutral endopeptidase inhibitor, and captopril in patients with chronic heart failure

“…This contributes to the reductiQln in left ventricular preload, but it has raised the concern that prolonged ANP infusion or endopeptidase inhibition might lead to the development of peripheral oedema [6]. However, we found no increase in oedema during 12 weeks candoxatril therapy, and no increase in body weight.…”

Effects of Exogenous and Endogenous Natriuretic Peptides on Forearm Vascular Function in Chronic Heart Failure

“…28 ANP infusion reduces cardiac filling pressures too rapidly to be solely accounted for by a fluid shift into the interstitial space and, in HF, in absence of significant diuresis or changes in hematocrit. 2,3,27 These observations re-emphasize the potentially important venous effects of ANP. Extending our previous findings in healthy controls, 16 the present study suggests that ANP also has important venodilator activity in cHF, but only modest effects on the resistance vasculature.…”

“…Systemic infusion of NP 8,27 (or elevation of endogenous NP by inhibiting their breakdown) 9 has been shown to increase stroke volume (SV) 27 and cardiac index 8 in patients with HF, despite a decrease in CVP, 8,9 a finding apparently in conflict with the Frank-Starling mechanism. This is almost certainly caused by a decrease in the volume of the right ventricle and a decrease in pericardial pressure, which increases effective LV distending pressure despite a decrease in LVEDP (ie, diastolic ventricular interaction).…”

Urodilatin: a new approach for the treatment of therapy‐resistant acute renal failure after liver transplantation

“…Until now, no other possibilities are offered to overcome this crucial problem except cyclosporine dose reduction in the early postoperative phase which include a higher risk of acute graft rejection. Results from experimental work in animals and humans [23,24] with CDD/ANP-99-126 and URO showed that these peptides could be tools to improve compromized renal function. It has been postulated that constriction of the preglomerular renal blood vessels induced by cyclosporine, catecholamines and angiotensin I1 and possibly also by endothelin is the main cause of renal deterioration [25].…”