Localization of angiotensin converting enzyme (kininase II). II. Immunocytochemistry and immunofluorescence

Ryan, Una S.; Ryan, James W.; Whitaker, Cecil; Chiu, Andrew T.

doi:10.1016/0040-8166(76)90025-2

Cited by 334 publications

(130 citation statements)

References 35 publications

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“…These findings do not bear out previous data indicating that the converting enzyme is mainly localized in vascular endothelium (Caldwell et al, 1976;Ryan et al, 1976). However, they are in good agreement with the results of more recent pharmacological and biochemical studies.…”

Section: Discussionsupporting

confidence: 70%

“…In particular, the endothelium of blood vessels has been shown to be a major site of conversion of AI to All by the converting enzyme located on its luminal surface (Caldwell et al, 1976;Ryan et al, 1976). Moreover, bovine aortic endothelial cells have been shown to contain renin and angiotensinogen and to be capable of synthesizing and secreting angiotensins (Lilly et al, 1985;Kifor & Dzau, 1987).…”

Section: Introductionmentioning

confidence: 99%

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Local formation of angiotensin II in the rat aorta: effect of endothelium

Eglème

Cressier

Wood

1990

British J Pharmacology

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1 The local formation of angiotensin II (All) from its precursors, angiotensin I (Al) and tetradecapeptide (TDP) renin substrate, was studied in intact (with endothelium) and rubbed (without endothelium) aortic rings of the rat. 2 AI and TDP renin substrate maximally contracted intact tissues in a similar way to All. The same observations were made in rubbed tissues. 3 The maximal response and the sensitivity of the aorta to these agonists were greater in rubbed than in intact tissues. 4 In intact preparations, methylene blue increased the contractile response to All and TDP to the same extent as endothelium removal. 5 In intact preparations, All receptor blockade completely suppressed all contractile responses, converting enzyme inhibition completely blocked the responses to AI and TDP, and renin inhibition partially blocked the responses to TDP. 6 In rubbed preparations, All receptor blockade completely inhibited all contractile responses, converting enzyme inhibition completely suppressed the responses to AI but only partially inhibited those to TDP, and renin inhibition partially blocked the responses to TDP. 7 In conclusion, the formation of All from TDP and its blockade by a converting enzyme inhibitor and a renin inhibitor shows that converting enzyme and a renin-like aspartic proteinase are present in the aortic wall. Furthermore, the results show that the endothelium is not essential for the conversion of the TDP to All, but modulates the responses to locally formed All through the release of endotheliumderived relaxing factor (EDRF).

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Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Local formation of angiotensin II in the rat aorta: effect of endothelium

Eglème

Cressier

Wood

1990

British J Pharmacology

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“…A second way in which vascular surface for conversion can increase is suggested by the ultrastructural studies of the endothelial cell surface by Ryan et al 13 They described numerous surface projections and indentations ("caveolae intracellulares") that are densely lined with converting enzyme. Thus, the amount of surface area with enzyme on it is increased by the complexity of these specialized surface adaptations.…”

Section: Discussionmentioning

confidence: 99%

Gestational changes in pulmonary converting enzyme activity in the fetal rabbit.

Stalcup¹,

Pang²,

Lipset³

et al. 1978

Circulation Research

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SUMMARY Changes in angiotensin-converting enzyme were measured in the lungs of fetal rabbits isolated and perfused in situ at varying ages from 22 days gestation to 7 days of age under controlled conditions of flow, pH, and temperature. Enzyme activity was assessed by infusing bradykinin or angiotensin I in Krebs-Henseleit solution and measuring residual peptide in the effluent by radioimmunoassay. The levels of substrate studied were below those required for enzyme saturation. Lungs of 22 day gestation fetuses removed only one-third of either peptide. The activity at term and in neonatal life resulted in more than 80% peptide removal. The time of the greatest rise in the percent substrate cleared occurs earlier than the time of the greatest increase in lung and body weight. The lower percentage of substrate cleared in early gestation appears to result in part from a limited surface area for enzyme activity in the primitive fetal pulmonary microvascular bed, since morphological studies with fluorescein-tagged anticonverting enzyme antibody demonstrated the presence of enzyme in the lung as early as 17 days of gestation. Electron micrographs of the pulmonary endothelial cell surface reveal that the degree of surface infolding and hence surface area increases with gestation. The higher percentage of substrate cleared in later gestation closely parallels the structural and ultrastructural development of the vascular bed. The presence of converting enzyme in the placenta by the second third of gestation and the large size of the placenta suggest that this organ may be a major locus of converting enzyme activity in the fetus.IMMATURITY of the lung and the consequent predisposition to neonatal respiratory distress syndrome (RDS) is a great risk to the survival of the prematurely born infant. In view of the role of the lungs in the clearance, activation, and release of vasoactive substances, 1 we hypothesized that immaturity of these functions prior to term birth is important in the pathogenesis of RDS, especially in the disorders of circulatory regulation and water balance seen in this disease. 2 Converting enzyme, a peptidyldipeptide hydrolase (EC 3.4.15.1) located on the plasma membrane of endothelial cells, degrades bradykinin (BK) and activates angiotensin I (A I) to angiotensin II (A II). 3 Both peptides have been assigned important roles in neonatal circulatory adaptations and transvascular fluid balance. 4 " 7 Studies in the fetal lamb have suggested a deficiency in converting enzyme in the fetus, 8 uration of converting enzyme activity in the lungs of fetal rabbits during the last third of gestation, and related this to the distribution of the enzyme as previously determined by immunofluorescence"' and to the complexity of the endothelial cell surface as revealed by electron micrographic techniques. MethodsOne hundred and one fetal New Zealand white rabbits, ranging in weight from 4 to 60 g, were obtained from 34 timed pregnancies and were studied at 22, 24, 25, 26, 28, 29, and 30 days of gestation. The fet...

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“…Antibodies to ACE have been used to demonstrate its localization in the pulmonary vascular endothelium (Ryan et al, 1976). More recently, Mendelsohn (1984) used '251 MK351A autoradiography to demonstrate the location of ACE in the central nervous system.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin‐converting Enzyme (Ace) Measurement in Human Serum Using Radioinhibitor Ligand Binding

Jackson

Cubela

Johnston

1986

Aust J Exp Biol Med

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Summary. MK315A, a tyrosyl analogue of enalaprilic acid (MK422) is a potent inhibitor of angiotensin-converting enzyme (ACE). MK351A was radioiodinated with '"i and used to develop a radioinhibitor binding assay for human serum ACE.'^'i MK351A associated rapidly and reversibly with human serum ACE (TVi = Vi h). Bound '"i MK351A was displaced by an excess of cold MK351A, to give non-specific binding of <1%. Scatchard analysis of binding was linear (r= -0-99, n = 6, p<0 001), indicating a single class of binding site.ACE was estimated in serum from normal patients and patients with sarcoid by the radio inhibitor binding assay and by enzyme kinetic assay using Hip-His-Leu as substrate. The two methods for ACE estimation correlated closely (r = 0-87, n«82, p< 0-001).The radioinhibitor binding assay for human serum ACE is a simple, sensitive and specific assay which utilizes novel assay methodology.

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Localization of angiotensin converting enzyme (kininase II). II. Immunocytochemistry and immunofluorescence

Cited by 334 publications

References 35 publications

Local formation of angiotensin II in the rat aorta: effect of endothelium

Local formation of angiotensin II in the rat aorta: effect of endothelium

Gestational changes in pulmonary converting enzyme activity in the fetal rabbit.

Angiotensin‐converting Enzyme (Ace) Measurement in Human Serum Using Radioinhibitor Ligand Binding

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