This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chappell, M. C. Articles by Ferrario, C. M. Search for Related Content PubMed PubMed Citation Articles by Chappell, M. C. Articles by Ferrario, C. M. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene Compound via MeSH Substance via MeSH Medline Plus Health Information Blood Pressure Medicines Hazardous Substances DB LISINOPRIL Related Collections ACE/Angiotension receptors Other Vascular biology

(Hypertension. 2000;35:348.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Release of Angiotensin-(1-7) From the Rat Hindlimb

Influence of Angiotensin-Converting Enzyme Inhibition

Mark C. Chappell; Martina N. Gomez; Nancy T. Pirro; Carlos M. Ferrario

From Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, NC.

Correspondence to Mark C. Chappell, PhD, Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1095. E-mail mchappel{at}wfubmc.edu

Abstract—The results of recent studies have demonstrated that angiotensin (Ang)-(1-7) contributes to the antihypertensive actions of either combined ACE/Ang II type 1 receptor blockade or ACE inhibition alone. The vasculature is a key site of action for either drug regimen, and evidence favors a local Ang system within these tissues. Because ACE may degrade Ang-(1-7), we determined whether ACE inhibition alters Ang-(1-7) release from the rat hindlimb perfused with Krebs-Ringer buffer containing Ficoll. Ang-(1-7) release averaged 36±13 fmol (period 1, 15-minute collection) and 44±11 fmol (period 2) in the control buffer. The addition of the ACE inhibitor lisinopril to the perfusion buffer augmented levels of Ang-(1-7) in periods 3 (144±39 fmol) and 4 (163±35 fmol; P<0.05 versus 1 or 2, n=8). HPLC and radioimmunoassay of effluent from control or lisinopril treatment demonstrated a single immunoreactive peak with a retention time identical to that of Ang-(1-7). The addition of the neprilysin inhibitor SCH 39370 reduced Ang-(1-7) release in the lisinopril buffer from 177±32 (period 1) and 173±39 (period 2) fmol to 112±24 (period 3) and 87±23 fmol (period 4; P<0.05 versus 1 or 2, n=6). Ang I metabolism in the collected perfusate revealed the formation of Ang-(1-7) that was sensitive only to thimet oligopeptidase inhibition; Ang II generation was not detected. The present study demonstrates the recovery of endogenous Ang-(1-7) from the perfused hindlimb. The release of Ang-(1-7) is significantly influenced by inhibition of ACE, which may reflect both increased substrate (Ang I) levels and reduced metabolism of the peptide. Neprilysin inhibition reduced but did not abolish Ang-(1-7) release, which suggests that other endopeptidases may contribute to the release of the peptide.

Key Words: angiotensin-converting enzyme • receptors, angiotensin II • angiotensin-(1-7)

This article has been cited by other articles:

				C. B. Herath, J. S. Lubel, Z. Jia, E. Velkoska, D. Casley, L. Brown, C. Tikellis, L. M. Burrell, and P. W. Angus Portal pressure responses and angiotensin peptide production in rat liver are determined by relative activity of ACE and ACE2 Am J Physiol Gastrointest Liver Physiol, July 1, 2009; 297(1): G98 - G106. [Abstract] [Full Text] [PDF]

				E. B. Oliveira, L. L. Souza, D. O. Sivieri Jr, L. B. Bispo-da-Silva, H. J. V. Pereira, C. M. Costa-Neto, M. V. Sousa, and M. C. O. Salgado Carboxypeptidase B and other kininases of the rat coronary and mesenteric arterial bed perfusates Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3550 - H3557. [Abstract] [Full Text] [PDF]

				A. Pignone, A. D. Rosso, K B. Brosnihan, F. Perfetto, R. Livi, G. Fiori, S. Guiducci, M. Cinelli, V. Rogai, A. Tempestini, et al. Reduced circulating levels of angiotensin-(1 7) in systemic sclerosis: a new pathway in the dysregulation of endothelial-dependent vascular tone control Ann Rheum Dis, October 1, 2007; 66(10): 1305 - 1310. [Abstract] [Full Text] [PDF]

				M. A. Cavasin, T.-D. Liao, X.-P. Yang, J. J. Yang, and O. A. Carretero Decreased Endogenous Levels of Ac-SDKP Promote Organ Fibrosis Hypertension, July 1, 2007; 50(1): 130 - 136. [Abstract] [Full Text] [PDF]

				K. D. Pendergrass, D. B. Averill, C. M. Ferrario, D. I. Diz, and M. C. Chappell Differential expression of nuclear AT1 receptors and angiotensin II within the kidney of the male congenic mRen2.Lewis rat Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1497 - F1506. [Abstract] [Full Text] [PDF]

				A. P. V. Dantas and K. Sandberg Regulation of ACE2 and ANG-(1-7) in the aorta: new insights into the renin-angiotensin system in the control of vascular function Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H980 - H981. [Full Text] [PDF]

				N. Li, J. Zimpelmann, K. Cheng, J. A. Wilkins, and K. D. Burns The role of angiotensin converting enzyme 2 in the generation of angiotensin 1-7 by rat proximal tubules Am J Physiol Renal Physiol, February 1, 2005; 288(2): F353 - F362. [Abstract] [Full Text] [PDF]

				J. G. Modrall, J. Sadjadi, K. B. Brosnihan, P. E. Gallagher, C.-h. Yu, G. L. Kramer, K. E. Bernstein, and M. C. Chappell Depletion of Tissue Angiotensin-Converting Enzyme Differentially Influences the Intrarenal and Urinary Expression of Angiotensin Peptides Hypertension, April 1, 2004; 43(4): 849 - 853. [Abstract] [Full Text] [PDF]

				J. Stegbauer, V. Oberhauser, O. Vonend, and L. C. Rump Angiotensin-(1-7) modulates vascular resistance and sympathetic neurotransmission in kidneys of spontaneously hypertensive rats Cardiovasc Res, February 1, 2004; 61(2): 352 - 359. [Abstract] [Full Text] [PDF]

				C. N. Shrimpton, A. I. Smith, and R. A. Lew Soluble Metalloendopeptidases and Neuroendocrine Signaling Endocr. Rev., October 1, 2002; 23(5): 647 - 664. [Abstract] [Full Text] [PDF]

				A. Nishiyama, D. M. Seth, and L. G. Navar Renal Interstitial Fluid Angiotensin I and Angiotensin II Concentrations during Local Angiotensin-Converting Enzyme Inhibition J. Am. Soc. Nephrol., September 1, 2002; 13(9): 2207 - 2212. [Abstract] [Full Text] [PDF]

				J. Xu, O. A. Carretero, Y.-H. Liu, E. G. Shesely, F. Yang, A. Kapke, and X.-P. Yang Role of AT2 Receptors in the Cardioprotective Effect of AT1 Antagonists in Mice Hypertension, September 1, 2002; 40(3): 244 - 250. [Abstract] [Full Text] [PDF]

				A. J. Allred, D. I. Diz, C. M. Ferrario, and M. C. Chappell Pathways for angiotensin-(1---7) metabolism in pulmonary and renal tissues Am J Physiol Renal Physiol, November 1, 2000; 279(5): F841 - F850. [Abstract] [Full Text] [PDF]