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Perindopril chronically inhibits angiotensin-converting enzyme in both the endothelium and adventitia of the internal mammary artery in patients with ischemic heart disease

ACE inhibitors are widely used in treating hypertension and heart failure, but the sites and mechanisms of ACE inhibition in human blood vessels are not understood. The present study was undertaken to assess the sites and extent of in vivo inhibition of ACE by long-term perindopril treatment in diff...

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Published in:Circulation (New York, N.Y.) N.Y.), 1997-07, Vol.96 (1), p.174-182
Main Authors: JIA LONG ZHUO, FROOMES, P, CASLEY, D, LIU, J. J, MURONE, C, CHAI, S. Y, BUXTON, B, MENDELSOHN, F. A. O
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container_start_page 174
container_title Circulation (New York, N.Y.)
container_volume 96
creator JIA LONG ZHUO
FROOMES, P
CASLEY, D
LIU, J. J
MURONE, C
CHAI, S. Y
BUXTON, B
MENDELSOHN, F. A. O
description ACE inhibitors are widely used in treating hypertension and heart failure, but the sites and mechanisms of ACE inhibition in human blood vessels are not understood. The present study was undertaken to assess the sites and extent of in vivo inhibition of ACE by long-term perindopril treatment in different layers of the internal mammary artery in patients with ischemic heart disease. Sixteen patients with ischemic heart disease were treated either with perindopril (4 mg/d PO) for up to 36 days before surgery (n = 9) or without the inhibitor as control subjects (n = 7). The segments of the internal mammary artery were collected for measurement of vascular free and total ACE by quantitative in vitro autoradiography with 125I-351A binding. The patients treated with perindopril had lower plasma ACE (P < .001) and plasma angiotensin (Ang) II-to-Ang I ratio (P < .05). In the internal mammary artery, free ACE was similarly inhibited by perindopril in the endothelium (P < .05) and adventitia (P < .05), and the free ACE-to-total ACE ratio, an index of ACE inhibition, was markedly decreased by perindopril in parallel in the endothelium (P < .001) and adventitia (P < .001). Moreover, plasma ACE correlated highly with vascular ACE in the endothelium (r = .85, P < .001) or adventitia (r = .78, P < .001), and mean arterial pressure correlated significantly with free ACE in the endothelium (r = .52, P < .05) or adventitia (r = .53, P < .05) and with the plasma Ang II-to-Ang I ratio (r = .53, P < .05). Light microscopic autoradiographs of 125I-351A binding revealed a marked inhibition of ACE by perindopril in both layers of the vascular wall. The present demonstrates that long-term administration of perindopril potently inhibits both endothelial and adventitial ACE to a comparable degree in the human internal mammary artery. These results indicate that perindopril effectively penetrates the vascular wall to inhibit ACE in the adventitia, thus providing evidence that perindopril may be beneficial in inhibiting both circulating Ang II and its local formation in the vascular wall.
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J ; MURONE, C ; CHAI, S. Y ; BUXTON, B ; MENDELSOHN, F. A. O</creator><creatorcontrib>JIA LONG ZHUO ; FROOMES, P ; CASLEY, D ; LIU, J. J ; MURONE, C ; CHAI, S. Y ; BUXTON, B ; MENDELSOHN, F. A. O</creatorcontrib><description><![CDATA[ACE inhibitors are widely used in treating hypertension and heart failure, but the sites and mechanisms of ACE inhibition in human blood vessels are not understood. The present study was undertaken to assess the sites and extent of in vivo inhibition of ACE by long-term perindopril treatment in different layers of the internal mammary artery in patients with ischemic heart disease. Sixteen patients with ischemic heart disease were treated either with perindopril (4 mg/d PO) for up to 36 days before surgery (n = 9) or without the inhibitor as control subjects (n = 7). The segments of the internal mammary artery were collected for measurement of vascular free and total ACE by quantitative in vitro autoradiography with 125I-351A binding. The patients treated with perindopril had lower plasma ACE (P < .001) and plasma angiotensin (Ang) II-to-Ang I ratio (P < .05). In the internal mammary artery, free ACE was similarly inhibited by perindopril in the endothelium (P < .05) and adventitia (P < .05), and the free ACE-to-total ACE ratio, an index of ACE inhibition, was markedly decreased by perindopril in parallel in the endothelium (P < .001) and adventitia (P < .001). Moreover, plasma ACE correlated highly with vascular ACE in the endothelium (r = .85, P < .001) or adventitia (r = .78, P < .001), and mean arterial pressure correlated significantly with free ACE in the endothelium (r = .52, P < .05) or adventitia (r = .53, P < .05) and with the plasma Ang II-to-Ang I ratio (r = .53, P < .05). Light microscopic autoradiographs of 125I-351A binding revealed a marked inhibition of ACE by perindopril in both layers of the vascular wall. The present demonstrates that long-term administration of perindopril potently inhibits both endothelial and adventitial ACE to a comparable degree in the human internal mammary artery. These results indicate that perindopril effectively penetrates the vascular wall to inhibit ACE in the adventitia, thus providing evidence that perindopril may be beneficial in inhibiting both circulating Ang II and its local formation in the vascular wall.]]></description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>PMID: 9236432</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams &amp; Wilkins</publisher><subject>Aged ; Angiotensin II - blood ; Angiotensin-Converting Enzyme Inhibitors - pharmacology ; Angiotensin-Converting Enzyme Inhibitors - therapeutic use ; Autoradiography ; Biological and medical sciences ; Cardiovascular system ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - enzymology ; Endothelium, Vascular - pathology ; Hemodynamics - drug effects ; Humans ; In Vitro Techniques ; Indoles - blood ; Indoles - pharmacology ; Indoles - therapeutic use ; Mammary Arteries - drug effects ; Mammary Arteries - enzymology ; Mammary Arteries - pathology ; Medical sciences ; Middle Aged ; Myocardial Ischemia - drug therapy ; Myocardial Ischemia - enzymology ; Myocardial Ischemia - pathology ; Peptidyl-Dipeptidase A - blood ; Perindopril ; Pharmacology. 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Sixteen patients with ischemic heart disease were treated either with perindopril (4 mg/d PO) for up to 36 days before surgery (n = 9) or without the inhibitor as control subjects (n = 7). The segments of the internal mammary artery were collected for measurement of vascular free and total ACE by quantitative in vitro autoradiography with 125I-351A binding. The patients treated with perindopril had lower plasma ACE (P < .001) and plasma angiotensin (Ang) II-to-Ang I ratio (P < .05). In the internal mammary artery, free ACE was similarly inhibited by perindopril in the endothelium (P < .05) and adventitia (P < .05), and the free ACE-to-total ACE ratio, an index of ACE inhibition, was markedly decreased by perindopril in parallel in the endothelium (P < .001) and adventitia (P < .001). Moreover, plasma ACE correlated highly with vascular ACE in the endothelium (r = .85, P < .001) or adventitia (r = .78, P < .001), and mean arterial pressure correlated significantly with free ACE in the endothelium (r = .52, P < .05) or adventitia (r = .53, P < .05) and with the plasma Ang II-to-Ang I ratio (r = .53, P < .05). Light microscopic autoradiographs of 125I-351A binding revealed a marked inhibition of ACE by perindopril in both layers of the vascular wall. The present demonstrates that long-term administration of perindopril potently inhibits both endothelial and adventitial ACE to a comparable degree in the human internal mammary artery. 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Drug treatments</topic><topic>Vasodilator agents. Cerebral vasodilators</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>JIA LONG ZHUO</creatorcontrib><creatorcontrib>FROOMES, P</creatorcontrib><creatorcontrib>CASLEY, D</creatorcontrib><creatorcontrib>LIU, J. J</creatorcontrib><creatorcontrib>MURONE, C</creatorcontrib><creatorcontrib>CHAI, S. Y</creatorcontrib><creatorcontrib>BUXTON, B</creatorcontrib><creatorcontrib>MENDELSOHN, F. A. 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O</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Perindopril chronically inhibits angiotensin-converting enzyme in both the endothelium and adventitia of the internal mammary artery in patients with ischemic heart disease</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>1997-07-01</date><risdate>1997</risdate><volume>96</volume><issue>1</issue><spage>174</spage><epage>182</epage><pages>174-182</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract><![CDATA[ACE inhibitors are widely used in treating hypertension and heart failure, but the sites and mechanisms of ACE inhibition in human blood vessels are not understood. The present study was undertaken to assess the sites and extent of in vivo inhibition of ACE by long-term perindopril treatment in different layers of the internal mammary artery in patients with ischemic heart disease. Sixteen patients with ischemic heart disease were treated either with perindopril (4 mg/d PO) for up to 36 days before surgery (n = 9) or without the inhibitor as control subjects (n = 7). The segments of the internal mammary artery were collected for measurement of vascular free and total ACE by quantitative in vitro autoradiography with 125I-351A binding. The patients treated with perindopril had lower plasma ACE (P < .001) and plasma angiotensin (Ang) II-to-Ang I ratio (P < .05). In the internal mammary artery, free ACE was similarly inhibited by perindopril in the endothelium (P < .05) and adventitia (P < .05), and the free ACE-to-total ACE ratio, an index of ACE inhibition, was markedly decreased by perindopril in parallel in the endothelium (P < .001) and adventitia (P < .001). Moreover, plasma ACE correlated highly with vascular ACE in the endothelium (r = .85, P < .001) or adventitia (r = .78, P < .001), and mean arterial pressure correlated significantly with free ACE in the endothelium (r = .52, P < .05) or adventitia (r = .53, P < .05) and with the plasma Ang II-to-Ang I ratio (r = .53, P < .05). Light microscopic autoradiographs of 125I-351A binding revealed a marked inhibition of ACE by perindopril in both layers of the vascular wall. The present demonstrates that long-term administration of perindopril potently inhibits both endothelial and adventitial ACE to a comparable degree in the human internal mammary artery. These results indicate that perindopril effectively penetrates the vascular wall to inhibit ACE in the adventitia, thus providing evidence that perindopril may be beneficial in inhibiting both circulating Ang II and its local formation in the vascular wall.]]></abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams &amp; Wilkins</pub><pmid>9236432</pmid><tpages>9</tpages></addata></record>
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identifier ISSN: 0009-7322
ispartof Circulation (New York, N.Y.), 1997-07, Vol.96 (1), p.174-182
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subjects Aged
Angiotensin II - blood
Angiotensin-Converting Enzyme Inhibitors - pharmacology
Angiotensin-Converting Enzyme Inhibitors - therapeutic use
Autoradiography
Biological and medical sciences
Cardiovascular system
Endothelium, Vascular - drug effects
Endothelium, Vascular - enzymology
Endothelium, Vascular - pathology
Hemodynamics - drug effects
Humans
In Vitro Techniques
Indoles - blood
Indoles - pharmacology
Indoles - therapeutic use
Mammary Arteries - drug effects
Mammary Arteries - enzymology
Mammary Arteries - pathology
Medical sciences
Middle Aged
Myocardial Ischemia - drug therapy
Myocardial Ischemia - enzymology
Myocardial Ischemia - pathology
Peptidyl-Dipeptidase A - blood
Perindopril
Pharmacology. Drug treatments
Vasodilator agents. Cerebral vasodilators
title Perindopril chronically inhibits angiotensin-converting enzyme in both the endothelium and adventitia of the internal mammary artery in patients with ischemic heart disease
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