Inactivation of atrial natriuretic factor by the renal brush border

Olins, Gillian M.; Spear, Kerry L.; Siegel, Ned R.; Zürcher‐Neely, Heidi A.

doi:10.1016/0005-2736(87)90260-4

Cited by 88 publications

(31 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ANF molecule is sufficiently small for filtration to occur and renal tubule brush border proteases have been reported to rapidly degrade ANF (33,34). In addition, receptors for ANF appear to be present in the renal vasculature and glomeruli (30) which may contribute in a small way to the removal of plasma ANF.…”

Section: Discussionmentioning

confidence: 99%

Clearance of atrial natriuretic factor by lung, liver, and kidney in human subjects and the dog.

Rodeheffer²,

et al. 1989

View full text Add to dashboard Cite

We determined human and canine plasma clearance of atrial natriuretic factor (ANF) by lung, liver, and kidney from arteriovenous differences in plasma ANF and measured organ plasma flow. Human subjects had lower plasma ANF concentrations in the pulmonary vein or the pulmonary capillary wedge position when compared with the pulmonary artery, and both sites yielded pulmonary ANF extraction ratios of 24%. Canine lung ANF extraction was 19±3% and pulmonary ANF clearance was 328±78 ml/min per m2 vs. 357±53 ml/min per mI in man. Hepatic plasma ANF clearance was 216±26 ml/ min with an extraction ratio of 30±3% in humans and 199±89 ml/min and 36±6% in the dog. Renal plasma ANF clearance in human subjects was 78±12 ml/min per kidney and correlated well with each kidney's creatinine clearance (r = 0.58, P < 0.05). The mean renal ANF extraction ratio was 35±4% in human subjects and 42±6% in the dog.These data quantitate the specific organ ANF clearances by lung, liver, and kidney in human subjects and in dogs and provide a rationale for elevated plasma ANF levels in cirrhosis, renal failure, and diseases accompanied by reduced perfusion of these organs. These findings support the conclusion that plasma ANF concentrations are dependent upon both the stimuli for ANF secretion as well as the specific organ clearances of ANF.

show abstract

Section: Discussionmentioning

confidence: 99%

Clearance of atrial natriuretic factor by lung, liver, and kidney in human subjects and the dog.

Rodeheffer²,

et al. 1989

View full text Add to dashboard Cite

show abstract

“…Preservation of the ANF ring structure is also critical for ANF bioactivity, and cleavage within the ring region at Asp 13 by a Staphylococcus protease abolishes ANF vasorelaxant activity (44). Indeed cleavage within the ANF ring at Cys 7 2Phe 8 , which leaves the disulfide bridge intact, is the primary ANF degradative cleavage occurring in the renal brush border (45). We illustrate in Table V that OpdB also cleaves ANF within the ring structure at Gly 10 Arg 11 2 Ile 12 .…”

mentioning

confidence: 99%

Oligopeptidase B from Trypanosoma evansi

Morty

Pellé

Vadász

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

, and plasma ANF levels inversely correlated with plasma OpdB activity. The in vitro halflife of ANF in rat plasma was reduced 300-fold in plasma from T. evansi-infected rodents, which contains high levels of OpdB activity. Addition of OpdB inhibitors to cell-free plasma from infected rodents significantly abrogated this ANF hydrolysis. Furthermore the in vivo ANF half-life was reduced 5-fold in T. evansi-infected rats. Thus, we propose a role for OpdB in peptide hormone dysregulation in trypanosomiasis, specifically in generating the depressed plasma levels of ANF in mammals infected with T. evansi.

show abstract

“…Long-term therapy requires either an orally active analogue or an inhibitor of ANP metabolism. Neutral endopeptidase (NEP) is a major ANP-degrading enzyme, [9][10][11] and a new therapeutic approach has been developed by inhibiting the enzyme and potentiating the effects of endogenous ANP. [12][13][14][15] Beneficial acute hemodynamic and renal effects of (±)-candoxatrilat (UK69578), an NEP inhibitor, have been reported in patients with congestive heart failure.…”

mentioning

confidence: 99%

Effect of Chronic Neutral Endopeptidase Inhibition on Cardiac Hypertrophy after Experimental Myocardial Infarction

et al. 1998

View full text Add to dashboard Cite

ongestive heart failure carries a grave prognosis, with a mortality rate of over 50% within 5 years of diagnosis. 1,2 The progressive nature of the disease is due in part to a series of neurohumoral homeostatic responses that initially maintain cardiac output and tissue perfusion but ultimately prove deleterious by increasing cardiac work and further reducing cardiac function. 3,4 These responses include enhancement of sympathetic tone, alteration in regional vascular resistance, activation of the renin-angiotensin-aldosterone system, and sodium retention.Atrial natriuretic peptide (ANP) is a peptide hormone of cardiac origin with multiple biologic effects including diuresis, natriuresis, vasodilatation, and inhibition of renin and aldosterone secretion. 5,6 Based on these properties, some studies have suggested a therapeutic role for ANP in congestive heart failure. 7,8 However, the therapeutic potential of ANP is limited by its peptidic nature and rapid elimination from circulation. Long-term therapy requires either an orally active analogue or an inhibitor of ANP metabolism. Neutral endopeptidase (NEP) is a major ANP-degrading enzyme, 9-11 and a new therapeutic approach has been developed by inhibiting the enzyme and potentiating the effects of endogenous ANP. 12-15 Beneficial acute hemodynamic and renal effects of (±)-candoxatrilat (UK69578), an NEP inhibitor, have been reported in patients with congestive heart failure. 12,13 Furthermore, reports about the effects of NEP inhibitors on cardiovascular remodeling have been published recently. 16,17 In patients with myocardial infarction, progressive left ventricular dilatation begins soon after myocardial infarction 18 and left ventricular volume is the most powerful predictor of prognosis. 19,20 In the rat model of chronic heart failure with coronary ligation, a time-dependent increase in ventricular volume was attenuated by chronic therapy with captopril, an angiotensin converting enzyme (ACE) inhibitor 21 and, moreover, therapy with captopril had a pronounced effect on survival. 22 The aim of this study was to examine whether chronic treatment with the NEP inhibitor candoxatril (UK79300) would modify cardiac hypertrophy in the rat model of myocardial infarction. Candoxatril is an orally active indanyl ester prodrug of the compound candoxatrilat (UK73967), the active isomer of the racemic mixture known as (±)-candoxatrilat (UK69578). 12,13 MethodsAdult male Sprague-Dawley rats (Biological Research Laboratories, Austin Hospital, Victoria, Australia) weighing about 300 g were used for this study. These animal studies conformed to the guiding principles of the NHMRC/CSIRO code of conduct and were approved by Effect of Chronic Neutral Endopeptidase Inhibition on Cardiac Hypertrophy after Experimental Myocardial InfarctionJpn Circ J 1998; 62: 680 -686 Kazunori Yoshida, MD; Minoru Yasujima, MD*; David J. Casley**; Colin I. Johnston, MD**Candoxatril is an inhibitor of neutral endopeptidase, a membrane-bound enzyme that degrades atrial natriuretic peptide. The ef...

show abstract

Inactivation of atrial natriuretic factor by the renal brush border

Cited by 88 publications

References 17 publications

Clearance of atrial natriuretic factor by lung, liver, and kidney in human subjects and the dog.

Clearance of atrial natriuretic factor by lung, liver, and kidney in human subjects and the dog.

Oligopeptidase B from Trypanosoma evansi

Effect of Chronic Neutral Endopeptidase Inhibition on Cardiac Hypertrophy after Experimental Myocardial Infarction

Contact Info

Product

Resources

About