AJP - Renal Watch the video to learn how APS reaches out to developing nations.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Renal Physiol 279: F841-F850, 2000;
0363-6127/00 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (36)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Allred, A. J.
Right arrow Articles by Chappell, M. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Allred, A. J.
Right arrow Articles by Chappell, M. C.
Vol. 279, Issue 5, F841-F850, November 2000

Pathways for angiotensin-(1---7) metabolism in pulmonary and renal tissues

Alicia J. Allred, Debra I. Diz, Carlos M. Ferrario, and Mark C. Chappell

Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157

Two of the primary sites of actions for angiotensin (ANG)-(1---7) are the vasculature and the kidney. Because little information exists concerning the metabolism of ANG-(1---7) in these tissues, we investigated the hydrolysis of the peptide in rat lung and renal brush-border membrane (BBM) preparations. Radiolabeled ANG-(1---7) was hydrolyzed primarily to ANG-(1---5) by pulmonary membranes. The ANG-converting enzyme (ACE) inhibitor lisinopril abolished the generation of ANG-(1---5), as well as that of smaller metabolites. Kinetic studies of the hydrolysis of ANG-(1---7) to ANG-(1---5) by somatic (pulmonary) and germinal (testes) forms of rat ACE yielded similar values, suggesting that the COOH-domain is responsible for the hydrolysis of ANG-(1---7). Pulmonary metabolism of ANG-(1---5) yielded ANG-(3---5) and was independent of ACE but may involve peptidyl or dipeptidyl aminopeptidases. In renal cortex BBM, ANG-(1---7) was rapidly hydrolyzed to mono- and dipeptide fragments and ANG-(1---4). Aminopeptidase (AP) inhibition attenuated the hydrolysis of ANG-(1---7) and increased ANG-(1---4) formation. Combined treatment with AP and neprilysin (Nep) inhibitors abolished ANG-(1---4) formation and preserved ANG-(1---7). ACE inhibition had no effect on the rate of hydrolysis or the metabolites formed in the BBM. In conclusion, ACE was the major enzymatic activity responsible for the metabolism of ANG-(1---7) in the lung, which is consistent with the ability of ACE inhibitors to increase the half-life of circulating ANG-(1---7) and raise endogenous levels of the peptide. An alternate pathway of metabolism was revealed in the renal cortex, where increased AP and Nep activities, relative to ACE activity, promote conversion of ANG-(1---7) to ANG-(1---4) and smaller fragments.

angiotensin-converting enzyme; neprilysin; lisinopril; SCH-39370; aminopeptidase; amastatin


This article has been cited by other articles:


Home page
 HypertensionHome page
H. A. Shaltout, J. P. Figueroa, J. C. Rose, D. I. Diz, and M. C. Chappell
Alterations in Circulatory and Renal Angiotensin-Converting Enzyme and Angiotensin-Converting Enzyme 2 in Fetal Programmed Hypertension
Hypertension, February 1, 2009; 53(2): 404 - 408.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
K. D. Pendergrass, N. T. Pirro, B. M. Westwood, C. M. Ferrario, K. B. Brosnihan, and M. C. Chappell
Sex differences in circulating and renal angiotensins of hypertensive mRen(2).Lewis but not normotensive Lewis rats
Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H10 - H20.
[Abstract] [Full Text] [PDF]

Home page
 Exp PhysiolHome page
I. Hamming, H. van Goor, A. J. Turner, C. A. Rushworth, A. A. Michaud, P. Corvol, and G. Navis
Differential regulation of renal angiotensin-converting enzyme (ACE) and ACE2 during ACE inhibition and dietary sodium restriction in healthy rats
Exp Physiol, May 1, 2008; 93(5): 631 - 638.
[Abstract] [Full Text] [PDF]

Home page
 Exp PhysiolHome page
P. J. Garabelli, J. G. Modrall, J. M. Penninger, C. M. Ferrario, and M. C. Chappell
Distinct roles for angiotensin-converting enzyme 2 and carboxypeptidase A in the processing of angiotensins within the murine heart
Exp Physiol, May 1, 2008; 93(5): 613 - 621.
[Abstract] [Full Text] [PDF]

Home page
 Exp PhysiolHome page
D. I. Diz, M. A. Garcia-Espinosa, S. Gegick, E. N. Tommasi, C. M. Ferrario, E. Ann Tallant, M. C. Chappell, and P. E. Gallagher
Injections of angiotensin-converting enzyme 2 inhibitor MLN4760 into nucleus tractus solitarii reduce baroreceptor reflex sensitivity for heart rate control in rats
Exp Physiol, May 1, 2008; 93(5): 694 - 700.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
C. Tikellis, K. Bialkowski, J. Pete, K. Sheehy, Q. Su, C. Johnston, M. E. Cooper, and M. C. Thomas
ACE2 Deficiency Modifies Renoprotection Afforded by ACE Inhibition in Experimental Diabetes
Diabetes, April 1, 2008; 57(4): 1018 - 1025.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
J. C. Sullivan
Sex and the renin-angiotensin system: inequality between the sexes in response to RAS stimulation and inhibition
Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2008; 294(4): R1220 - R1226.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
J. Joyner, L. A. A. Neves, J. P. Granger, B. T. Alexander, D. C. Merrill, M. C. Chappell, C. M. Ferrario, W. P. Davis, and K. B. Brosnihan
Temporal-spatial expression of ANG-(1-7) and angiotensin-converting enzyme 2 in the kidney of normal and hypertensive pregnant rats
Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R169 - R177.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
P. E. Gallagher, M. C. Chappell, C. M. Ferrario, and E. A. Tallant
Distinct roles for ANG II and ANG-(1-7) in the regulation of angiotensin-converting enzyme 2 in rat astrocytes
Am J Physiol Cell Physiol, February 1, 2006; 290(2): C420 - C426.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
C. M. Ferrario, A. J. Trask, and J. A. Jessup
Advances in biochemical and functional roles of angiotensin-converting enzyme 2 and angiotensin-(1-7) in regulation of cardiovascular function
Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2281 - H2290.
[Abstract] [Full Text] [PDF]

Home page
 Exp PhysiolHome page
M. J. Katovich, J. L. Grobe, M. Huentelman, and M. K. Raizada
Angiotensin-converting enzyme 2 as a novel target for gene therapy for hypertension
Exp Physiol, May 1, 2005; 90(3): 299 - 305.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
R. A. S. Santos, A. J. Ferreira, A. P. Nadu, A. N. G. Braga, A. P. de Almeida, M. J. Campagnole-Santos, O. Baltatu, R. Iliescu, T. L. Reudelhuber, and M. Bader
Expression of an angiotensin-(1-7)-producing fusion protein produces cardioprotective effects in rats
Physiol Genomics, May 19, 2004; 17(3): 292 - 299.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
V.V Petrov, R.H Fagard, and P.J Lijnen
Arginine-aminopeptidase in rat cardiac fibroblastic cells participates in angiotensin peptide turnover
Cardiovasc Res, March 1, 2004; 61(4): 724 - 735.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online