Specific inhibitors of endopeptidase 24.11 inhibit the metabolism of atrial natriuretic peptides in vitro and in vivo

1989 ◽  
Vol 61 (2) ◽  
pp. 201-208 ◽  
Author(s):  
Gillian M. Olins ◽  
Philip A. Krieter ◽  
Angelo J. Trapani ◽  
Kerry L. Spear ◽  
Philippe R. Bovy
Life Sciences ◽  
1989 ◽  
Vol 45 (10) ◽  
pp. 869-875 ◽  
Author(s):  
J.-P. Stasch ◽  
C. Birth-Dietrich ◽  
S. Kazda ◽  
D. Neuser

Hypertension ◽  
1985 ◽  
Vol 7 (6_pt_1) ◽  
pp. 905-912 ◽  
Author(s):  
N C Trippodo ◽  
A Januszewicz ◽  
B L Pegram ◽  
F E Cole ◽  
N Kohashi ◽  
...  

1996 ◽  
Vol 60 (5) ◽  
pp. 300-310 ◽  
Author(s):  
Quan Liu ◽  
Ichiro Nakae ◽  
Takayoshi Tsutamoto ◽  
Atsushi Takaoka ◽  
Masahiko Kinoshita

1988 ◽  
Vol 254 (2) ◽  
pp. 531-537 ◽  
Author(s):  
Y Vanneste ◽  
A Michel ◽  
R Dimaline ◽  
T Najdovski ◽  
M Deschodt-Lanckman

alpha-Human atrial natriuretic peptide (hANP) is secreted by the heart and acts on the kidney to promote a strong diuresis and natriuresis. In vivo it has been shown to be catabolized partly by the kidney. Crude microvillar membranes of human kidney degrade 125I-ANP at several internal bonds generating metabolites among which the C-terminal fragments were identified. Formation of the C-terminal tripeptide was blocked by phosphoramidon, indicating the involvement of endopeptidase-24.11 in this cleavage. Subsequent cleavages by aminopeptidase(s) yielded the C-terminal dipeptide and free tyrosine. Using purified endopeptidase 24.11, we identified seven sites of hydrolysis in unlabelled alpha-hANP: the bonds Arg-4-Ser-5, Cys-7-Phe-8, Arg-11-Met-12, Arg-14-Ile-15, Gly-16-Ala-17, Gly-20-Leu-21 and Ser-25-Phe-26. However, the bonds Gly-16-Ala-17 and Arg-4-Ser-5 did not fulfil the known specificity requirements of the enzyme. Cleavage at the Gly-16-Ala-17 bond was previously observed by Stephenson & Kenny [(1987) Biochem. J. 243, 183-187], but this is the first report of an Arg-Ser bond cleavage by this enzyme. Initial attack of alpha-hANP by endopeptidase-24.11 took place at a bond within the disulphide-linked loop and produced a peptide having the same amino acid composition as intact ANP. The bond cleaved in this metabolite was determined as the Cys-7-Phe-8 bond. Determination of all the bonds cleaved in alpha-hANP by endopeptidase-24.11 should prove useful for the design of more stable analogues, which could have therapeutic uses in hypertension.


1997 ◽  
Vol 273 (2) ◽  
pp. R527-R539 ◽  
Author(s):  
K. R. Olson ◽  
D. J. Conklin ◽  
A. P. Farrell ◽  
J. E. Keen ◽  
Y. Takei ◽  
...  

Active venous regulation of cardiovascular function is well known in mammals but has not been demonstrated in fish. In the present studies, the natriuretic peptides (NP) rat atrial natriuretic peptide (ANP) and trout ventricular natriuretic peptide (VNP), clearance receptor inhibitor SC-46542, and sodium nitroprusside (SNP) were infused into unanesthetized trout fitted with pressure cannulas in the ventral aorta, dorsal aorta, and ductus Cuvier, and a ventral aorta (VA) flow probe was used to measure cardiac output (CO). In another group, in vivo vascular (venous) capacitance curves were obtained during ANP or SNP infusion. The in vitro effects of NP on vessels and the heart were also examined. ANP, VNP, and SC-46542 decreased central venous pressure (PVen), CO, stroke volume (SV), and gill resistance (RG), whereas systemic resistance (RS) and heart rate (HR) increased. Dorsal aortic pressure (PDA) transiently increased and then fell even though RS remained elevated. ANP decreased mean circulatory filling pressure (MCFP), increased vascular compliance at all blood volumes, and increased unstressed volume in hypovolemic fish. ANP had no direct effect on the heart. ANP responses in vivo were not altered in trout made hypotensive by prior treatment with the angiotensin-converting enzyme inhibitor lisinopril. SNP reduced ventral aortic pressure (PVA), PDA, and RS, increased CO and HR, but did not affect PVen, SV, or RG. SNP slightly decreased MCFP but did not affect compliance or unstressed volume. In vitro, large systemic arteries were more responsive than veins to NP, whereas SNP relaxed both. These results show that, in vivo, NP decrease venous compliance, thereby decreasing venous return, CO, and arterial pressure. Conversely, SNP hypotension is due to decreased RS. This is the first evidence for active regulation of venous capacitance in fish, which probably occurs in small veins or venules. The presence of venous baroreceptors is also suggested.


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