Degradation and clearance of atrial natriuretic factors (ANF)

Gerbes, Alexander L.; Vollmar, Angelika M.

doi:10.1016/0024-3205(90)90208-9

Cited by 46 publications

(18 citation statements)

References 85 publications

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“…An increase of plasma ET-3 could therefore be interpreted as a result of stimulated synthesis and release following sympathetic activation. On the other hand, ET-3 elevations could contribute to the vasodilation in cirrhosis and thus stimulate an activation of the sympathetic nervous system, Plasma concentrations of peptides are determined not only by synthesis and release, but also by clearance and degradation (14). Therefore, another mechanism leading to increased ET-3 plasma levels could be a decreased renal clearance of ET-3, as described in patients undergoing chronic hemodialysis (15).…”

Section: Discussionmentioning

confidence: 99%

Endothelin-3 like immunoreactivity in plasma of patients with cirrhosis of the liver

Gülberg¹,

Gerbes²,

Vollmar

et al. 1992

Life Sciences

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SummaryA highly specific and sensitive radioimmunoassay (R/A) has been established for determination of endothelin-3 like immunoreactivity in human plasma to investigate its possible role in hemodynamic alterations due to liver disease. Crossreactivity with other endothelin isoforms was always below 4 %, the lower detection limit following extraction on Sep-Pak C18 cartridges was 0.5 pg/ml. The concentration of endothelin-3 (mean + SEM) was 4.16 + 0.56 pg/ml (n = 13) in plasma of patients with cirrhosis of the liver, three fold higher than in age matched controls (1.35 + 0.27 pg/ml, n = 12, p < 0.01). Plasma immunoreactivity was confirmed to be endothelin-3 related by reverse-phase HPLC. These data could suggest a role of plasma endothelin-3 in circulatory changes, as they occur in cirrhosis of the liver.Endothelin-1 (ET-I), a 21 amino acid peptide with potent vasoconstrictor activity (I) has been investigated in a variety of cardiovascular and endocrine diseases to establish its possible role in the pathophysiology of these disorders (for review see 2,3). As yet there is only scarce information about endothelin-3 (ET-3) which differs from ET-1 by six amino acids (4). However, determination of circulating ET-3 is of considerable interest regarding the different pharmacological properties of ET-3 and ET-1 (4-6). ET-3 has been shown to act as a vasodilator (7,8) and therefore may play a role different from ET-1 in various pathophysiological conditions. Hemodynamic changes in cirrhosis of the liver are characterized by peripheral vasodilation (9), however the responsible agent has not been identified so far. Vasodilating substances which are released into the intestinal circulation and cleared to a lesser extent by the cirrhotic liver are candidates in this respect. Since the intestine has been shown to be a major site of ET-3 synthesis (10) one might speculate, that ET-3 plasma levels could be increased in chronic fiver disease, thus contributing to the aforementioned hemodynamic alterations. Therefore we established a RIA to investigate circulating ET-3 in patients with cirrhosis of the liver.

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Section: Discussionmentioning

confidence: 99%

Endothelin-3 like immunoreactivity in plasma of patients with cirrhosis of the liver

Gülberg¹,

Gerbes²,

Vollmar

et al. 1992

Life Sciences

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“…Moreover, difficulties in sampling arise with pulmonary venous catheterization. Finally, in several studies, organ blood flow is not taken into consideration (56).…”

Section: Anf Clearance By the Lungsmentioning

confidence: 99%

Role of atrial natriuretic factor in lung physiology and pathology.

Perreault¹,

Gutkowska²

1995

Am J Respir Crit Care Med

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“…Despite chronically increased levels of, and an apparent tolerance to the effects of this peptide, plasma ANF concentration in heart failure patients has been shown to acutely respond to alterations in central filling pressures [4], In addition, intravenous administration of pharmacological doses of ANF produces salutary hemo dynamic and renal effects in such patients [5,6], Due to the impracticality and expense of chronic administration of exogenous ANF, recent investigation in animals with experimentally induced CHF and in hu mans with mild impairment in left ventricular perfor mance has focused on alteration of the metabolism of ANF [7,8], These studies suggest that therapeutic benefit can be achieved through the inhibition of the renal metab olism of ANF. Plasma ANF concentration is reduced by more than 50% during one passage across the kidney, where it is degraded primarily by the action of neutral endopeptidase, a nonsaturable enzyme present in high concentration within the brush border of the proximal renal tubule [9],…”

Section: Introductionmentioning

confidence: 99%

Effects of Renal Neutral Endopeptidase Inhibition on Sodium Excretion, Renal Hemodynamics and Neuro-hormonal Activation in Patients with Congestive Heart Failure

Kimmelstiel¹,

Perrone

Kilcoyne³

et al. 1996

Cardiology

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We investigated the effects of inhibiting endogenous atrial natriuretic factor (ANF) metabolism on renal hemodynamics, sodium excretion and neurohormones in 12 patients with New York Heart Association functional class II congestive heart failure (CHF) due to left ventricular systolic dysfunction. In a randomized, placebo-controlled, double-blinded fashion, 8 patients received a single oral dose of candoxatril, an inhibitor of renal neutral endopeptidase, and 4 patients received placebo. Candoxatril treatment increased plasma ANF by 70 ± 71 pg/ml (p < 0.015 vs. placebo) and plasma cGMP by 7.9 ± 2.7 pmol/ml (p < 0.001 vs. placebo), with maximal effects at 3.5 h. Urinary cGMP more than doubled (p = 0.025 vs. placebo). Candoxatril increased urinary sodium by 2.7 ± 2.0 mEq/h (p < 0.05 vs. placebo) and significantly elevated filtration fraction with no significant effect on glomerular filtration rate, renal plasma flow or lithium clearance. A significant reduction in aldosterone concentration with a similar trend in plasma renin activity was noted in can-doxatril-treated patients. Thus in patients with moderate heart failure, renal neutral endopeptidase inhibition increases urinary sodium excretion. The lack of an effect on renal hemodynamics suggests that this natriuresis results from ANF-mediated inhibition of tubular sodium reabsorption. These findings justify additional investigation into potential clinical benefit of endopeptidase inhibition in patients with CHF.

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Degradation and clearance of atrial natriuretic factors (ANF)

Cited by 46 publications

References 85 publications

Endothelin-3 like immunoreactivity in plasma of patients with cirrhosis of the liver

Endothelin-3 like immunoreactivity in plasma of patients with cirrhosis of the liver

Role of atrial natriuretic factor in lung physiology and pathology.

Effects of Renal Neutral Endopeptidase Inhibition on Sodium Excretion, Renal Hemodynamics and Neuro-hormonal Activation in Patients with Congestive Heart Failure

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