Neutral metalloendopeptidase inhibitors as ANF potentiators: sites and mechanisms of action

1991 ◽  
Vol 69 (10) ◽  
pp. 1628-1635 ◽  
Author(s):  
Edmund J. Sybertz Jr. ◽  
Peter J. S. Chiu ◽  
Robert W. Watkins ◽  
Subbarao Vemulapalli
Keyword(s):  
Atrial Natriuretic Factor ◽  
Polyclonal Antiserum ◽  
Antihypertensive Activity ◽  
Natriuretic Factor ◽  
Bradykinin Antagonist ◽  
Desoxycorticosterone Acetate ◽  
Antihypertensive Response ◽  
Permissive Role ◽  
Atrial Natriuretic

Inhibition of the enzyme neutral metalloendopeptidase potentiates responses to atrial natriuretic factor and elicits reductions of blood pressure in desoxycorticosterone acetate sodium hypertensive rats. The present study evaluated the role of atrial natriuretic factor and bradykinin in the antihypertensive response to neutral metalloendopeptidase inhibition through the use of antibodies and antagonists, respectively. In addition, the pharmacokinetic mechanism by which neutral metalloendopeptidase inhibition interferes with atrial natriuretic factor metabolism was explored. The antihypertensive response to the neutral metalloendopeptidase inhibitor SCH 34826 was abruptly reversed by i.v. injection of a polyclonal antiserum to atrial natriuretic factor. In contrast, the antihypertensive response to SCH 34826 was unaffected by injection of the bradykinin antagonist Thi5,8-D-Phe7 bradykinin. The renal response to atrial natriuretic factor, SCH 34826, and phosphoramidon was inhibited by the bradykinin antagonist. The NEP inhibitor SCH 39370 significantly delayed the disappearance of TCA precipitable radioactivity from plasma following i.v. bolus dosing with 125I-labelled ANF 99–126. The effects were enhanced in the presence of the C receptor ligand. The results indicate that atrial natriuretic factor, but not bradykinin, plays an important role in the antihypertensive response to SCH 34826. Bradykinin plays a permissive role in the diuretic responses to atrial natriuretic factor and inhibitors of neutral metalloendopeptidase. Lastly, neutral metalloendopeptidase inhibition significantly alters the clearance and metabolism of tracer quantities of atrial natriuretic factor.Key words: neutral metalloendopeptidase, SCH 34826, bradykinin, SCH 39370, atrial natriuretic factor metabolism, antihypertensive activity.

Role of potassium channels in stretch-promoted atrial natriuretic factor secretion

2009 ◽  
Vol 3 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Tsuneo Ogawa ◽  
Monica Forero ◽  
Patrick G. Burgon ◽  
Mercedes L. Kuroski de Bold ◽  
Tina Georgalis ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Atrial Natriuretic Factor ◽  
Natriuretic Factor ◽  
Factor Secretion ◽  
Atrial Natriuretic

Atrial natriuretic factor and renal function during head-out water immersion in conscious dogs

1986 ◽  
Vol 251 (5) ◽  
pp. R1000-R1004
Author(s):  
K. Miki ◽  
G. Hajduczok ◽  
M. R. Klocke ◽  
J. A. Krasney ◽  
S. K. Hong ◽  
...  
Keyword(s):  
Sodium Excretion ◽  
Atrial Natriuretic Factor ◽  
Time Course ◽  
Water Immersion ◽  
Base Line ◽  
Peripheral Tissues ◽  
Natriuretic Factor ◽  
Peak Value ◽  
Atrial Natriuretic

The potential role of atrial natriuretic factor (ANF) in the renal response to head-out water immersion (WI) was studied. Five female mongrel dogs, trained to stand for 100 min in air followed by 100 min of thermoneutral WI at 37 degrees C or 200 min in air (timed control, TC), were chronically instrumented with arterial and venous catheters. The animals were hydrated with a volume of 0.45% NaCl solution equivalent to 2% of their body weight. Prehydration levels of arterial ANF were 243 +/- 15 (SE), and venous ANF levels were 211 +/- 21 pg/ml. WI resulted in an increase in urine flow from 0.7 +/- 0.1 ml/min to a peak flow of 2.2 +/- 0.3 ml/min (P less than 0.05). On immersion, plasma venous and arterial ANF levels increased significantly by 29 and 21% from the preimmersion values of 183 +/- 14 and 222 +/- 20 pg/ml, respectively. The arterial-venous difference for plasma ANF was maintained at 35 +/- 14 pg/ml (P less than 0.05) during WI; therefore venous sampling may suffice as a measure of circulating ANF levels. Sodium excretion increased linearly during WI to a peak value of 228 +/- 32 mu eq/min from a base line of 52 +/- 12 mu eq/min (P less than 0.05). These data indicate that peripheral tissues extract ANF and that WI is a physiological stimulus for the release of ANF. However, the time course and magnitude of the changes in plasma ANF and urine sodium excretion during WI are not comparable, and other mechanisms are likely responsible for the WI natriuresis.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Role of prostaglandins in mediating the renal effects of atrial natriuretic factor.

Hypertension ◽  
1988 ◽  
Vol 12 (3) ◽  
pp. 274-278 ◽  
Author(s):  
F J Salazar ◽  
R Bolterman ◽  
M J Fiksen-Olsen ◽  
T Quesada ◽  
J C Romero
Keyword(s):  
Atrial Natriuretic Factor ◽  
Renal Effects ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

Responses of vasoactive hormones in congestive cardiac failure

1987 ◽  
Vol 65 (8) ◽  
pp. 1706-1711 ◽  
Author(s):  
C. I. Johnston ◽  
L. F. Arnolda ◽  
K. Tsunoda ◽  
P. A. Phillips ◽  
G. P. Hodsman
Keyword(s):  
Heart Failure ◽  
Cardiac Failure ◽  
Atrial Natriuretic Factor ◽  
Peripheral Resistance ◽  
Congestive Cardiac Failure ◽  
Renin Angiotensin ◽  
Natriuretic Factor ◽  
Vasoactive Hormones ◽  
Atrial Natriuretic

Congestive cardiac failure causes activation of various neurohumoral responses that increase total peripheral resistance and promote salt and water retention. These effects increase blood pressure and organ perfusion in the short term, but ultimately cause further cardiac decompensation by increasing ventricular afterload and cardiac work. The role of the renin–angiotensin–aldosterone system and the catecholamines is partially understood, and blockade of these systems as a treatment of heart failure is now established. The role of vasopressin in heart failure is more controversial, but there is now compelling evidence that vasopressin may have important vasoconstrictor actions in addition to its fluid retaining properties. Atrial natriuretic factor is a newly described cardiac hormone released from the atrium. Atrial natriuretic factor causes natriuresis, diuresis, vasodilatation, suppression of thirst, and suppression of both renin and aldosterone. These actions largely counteract the effects of the renin–angiotensin system and vasopressin. Plasma atrial natriuretic factor has been reported to be markedly elevated in human and experimental heart failure, and may act to limit the neurohumoral response to reduced cardiac output. This review summarizes our understanding of the vasoactive hormones and reports experimental evidence supporting a pathophysiological role for vasopressin and atrial natriuretic factor in congestive cardiac failure.

Low-dose endothelin-1 potentiates volume-induced secretion of atrial natriuretic factor

1992 ◽  
Vol 263 (3) ◽  
pp. H939-H944 ◽  
Author(s):  
J. Donckier ◽  
C. Hanet ◽  
L. Galanti ◽  
L. Stoleru ◽  
H. Van Mechelen ◽  
...  
Keyword(s):  
Heart Rate ◽  
Atrial Natriuretic Factor ◽  
Left Atrial ◽  
Low Dose ◽  
Endothelin 1 ◽  
Natriuretic Factor ◽  
Free Intracellular Calcium ◽  
Phosphoinositide Pathway ◽  
Atrial Natriuretic

To evaluate the role of calcium in volume-induced secretion of atrial natriuretic factor (ANF), effects of verapamil and endothelin-1 (ET-1), both known to influence free intracellular calcium, were studied during saline infusion in seven conscious instrumented dogs. Fifteen minutes after intravenous injection of placebo or verapamil (0.25 mg/kg) or during continuous ET-1 infusion (at 5 ng.kg-1.min-1), saline (10% body wt) was infused during 40 min. Saline produced a rise (P less than 0.001) of plasma ANF from 28.1 +/- 6.3 to 50.4 +/- 12.9 pM after placebo, from 30.2 +/- 6.1 to 51.1 +/- 8.5 pM after verapamil, and from 31.2 +/- 6.1 to 81.0 +/- 12.9 pM with ET-1. This increase was comparable after placebo and verapamil, but was 80% greater with ET-1 (P less than 0.02). Plasma ET-1, unchanged after placebo, rose (P less than 0.001) from 1.7 +/- 0.5 to 38.3 +/- 9.2 pM with ET-1. In the three experiments, heart rate and left atrial pressure (LAP) increased (P less than 0.001) similarly. The linear relation between ANF and LAP was steeper with ET-1 than with saline or verapamil (both P less than 0.05), indicating that the enhanced ANF secretion with ET-1 was occurring at all levels of LAP. Thus volume-induced secretion of ANF is not suppressed by verapamil, but is directly enhanced by low-dose ET-1, known to activate the phosphoinositide pathway.

scholarly journals Role of the liver in splanchnic extraction of atrial natriuretic factor in the rat

Hepatology ◽  
1992 ◽  
Vol 16 (3) ◽  
pp. 790-793 ◽  
Author(s):  
Alexander L. Gerbes ◽  
Rochus Witthaut ◽  
Veit Gülberg ◽  
Gaétan Thibault ◽  
Manfred Bilzer ◽  
...  
Keyword(s):  
Atrial Natriuretic Factor ◽  
Natriuretic Factor ◽  
Atrial Natriuretic
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