Acute and Chronic In Vivo Inhibition of Angiotensin-Converting Enzyme by Perindopril in the Endothelium and Adventitia of Large Arteries and Organs of the Rabbit

Angiotensin-converting enzyme (ACE) inhibitors are widely used in treating hypertension and chronic heart failure, but their precise sites and mechanisms of the actions are not completely understood. In this study, we evaluated the acute and chronic in vivo inhibition of ACE by perindopril in both t...

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Veröffentlicht in:Journal of cardiovascular pharmacology 1997-03, Vol.29 (3), p.297-310
Hauptverfasser: Zhuo, Jialong, Casley, David, Murone, Carmel, Mendelsohn, Frederick A. O
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Murone, Carmel
Mendelsohn, Frederick A. O
description Angiotensin-converting enzyme (ACE) inhibitors are widely used in treating hypertension and chronic heart failure, but their precise sites and mechanisms of the actions are not completely understood. In this study, we evaluated the acute and chronic in vivo inhibition of ACE by perindopril in both the endothelium and adventitia of large blood vessels including the aorta, carotid, and femoral arteries, heart, lung, and kidney by using in vitro autoradiography with [I]351A as a ligand. After short-term (0.1, 0.3, and 1 mg/kg) or long-term oral admin-istration (0.3 mg/kg), perindopril significantly inhibited plasma ACE (p < 0.001), the plasma angiotensin II (Ang II)/Ang I ratio (p < 0.01), and decreased mean arterial pressure (p < 0.001) in a dose-related manner. In the aorta, carotid, and femoral arteries, free ACE was inhibited to a similar extent in both the endthelium and adventitia by perindopril, in a dose-dependent manner, whereas total ACE in both layers of these vessels was unaltered. Similar short- and long-term ACE inhibition by perindopril was observed in the lung and heart, with somewhat greater inhibition of kidney and plasma ACE. Vascular and tissue ACE inhibition correlated highly with both plasma ACE and the plasma Ang II/Ang I ratio (r = 0.63-0.89; p < 0.001). Whereas the effects of perindopril on blood pressure, plasma Ang II/Ang I ratio, plasma and vascular ACE were all highly dose dependent, there were no significant differences on the degree of ACE inhibition observed between the three large blood vessels or between their adventitial and endothelial layers. These results demonstrate that perindopril readily penetrates the vascular wall after short- or long-term oral administration, and in a dose-dependent manner, potently inhibits both endothelial and advential vascular ACE to a comparable degree. Therefore ACE inhibitors may be beneficial in inhibiting both circulating Ang II and its local formation in the vascular wall.
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In the aorta, carotid, and femoral arteries, free ACE was inhibited to a similar extent in both the endthelium and adventitia by perindopril, in a dose-dependent manner, whereas total ACE in both layers of these vessels was unaltered. Similar short- and long-term ACE inhibition by perindopril was observed in the lung and heart, with somewhat greater inhibition of kidney and plasma ACE. Vascular and tissue ACE inhibition correlated highly with both plasma ACE and the plasma Ang II/Ang I ratio (r = 0.63-0.89; p &lt; 0.001). Whereas the effects of perindopril on blood pressure, plasma Ang II/Ang I ratio, plasma and vascular ACE were all highly dose dependent, there were no significant differences on the degree of ACE inhibition observed between the three large blood vessels or between their adventitial and endothelial layers. These results demonstrate that perindopril readily penetrates the vascular wall after short- or long-term oral administration, and in a dose-dependent manner, potently inhibits both endothelial and advential vascular ACE to a comparable degree. 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O</creatorcontrib><title>Acute and Chronic In Vivo Inhibition of Angiotensin-Converting Enzyme by Perindopril in the Endothelium and Adventitia of Large Arteries and Organs of the Rabbit</title><title>Journal of cardiovascular pharmacology</title><addtitle>J Cardiovasc Pharmacol</addtitle><description>Angiotensin-converting enzyme (ACE) inhibitors are widely used in treating hypertension and chronic heart failure, but their precise sites and mechanisms of the actions are not completely understood. In this study, we evaluated the acute and chronic in vivo inhibition of ACE by perindopril in both the endothelium and adventitia of large blood vessels including the aorta, carotid, and femoral arteries, heart, lung, and kidney by using in vitro autoradiography with [I]351A as a ligand. After short-term (0.1, 0.3, and 1 mg/kg) or long-term oral admin-istration (0.3 mg/kg), perindopril significantly inhibited plasma ACE (p &lt; 0.001), the plasma angiotensin II (Ang II)/Ang I ratio (p &lt; 0.01), and decreased mean arterial pressure (p &lt; 0.001) in a dose-related manner. In the aorta, carotid, and femoral arteries, free ACE was inhibited to a similar extent in both the endthelium and adventitia by perindopril, in a dose-dependent manner, whereas total ACE in both layers of these vessels was unaltered. Similar short- and long-term ACE inhibition by perindopril was observed in the lung and heart, with somewhat greater inhibition of kidney and plasma ACE. Vascular and tissue ACE inhibition correlated highly with both plasma ACE and the plasma Ang II/Ang I ratio (r = 0.63-0.89; p &lt; 0.001). Whereas the effects of perindopril on blood pressure, plasma Ang II/Ang I ratio, plasma and vascular ACE were all highly dose dependent, there were no significant differences on the degree of ACE inhibition observed between the three large blood vessels or between their adventitial and endothelial layers. These results demonstrate that perindopril readily penetrates the vascular wall after short- or long-term oral administration, and in a dose-dependent manner, potently inhibits both endothelial and advential vascular ACE to a comparable degree. Therefore ACE inhibitors may be beneficial in inhibiting both circulating Ang II and its local formation in the vascular wall.</description><subject>Angiotensin I - blood</subject><subject>Angiotensin II - blood</subject><subject>Angiotensin-Converting Enzyme Inhibitors - pharmacology</subject><subject>Animals</subject><subject>Aorta - drug effects</subject><subject>Aorta - enzymology</subject><subject>Arteries - drug effects</subject><subject>Arteries - enzymology</subject><subject>Autoradiography</subject><subject>Biological and medical sciences</subject><subject>Blood Pressure - drug effects</subject><subject>Cardiovascular system</subject><subject>Carotid Arteries - drug effects</subject><subject>Carotid Arteries - enzymology</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - enzymology</subject><subject>Femoral Artery - drug effects</subject><subject>Femoral Artery - enzymology</subject><subject>Indoles - pharmacology</subject><subject>Kidney - enzymology</subject><subject>Lung - enzymology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Myocardium - enzymology</subject><subject>Peptidyl-Dipeptidase A - blood</subject><subject>Peptidyl-Dipeptidase A - metabolism</subject><subject>Perindopril</subject><subject>Pharmacology. Drug treatments</subject><subject>Rabbits</subject><subject>Renin - blood</subject><issn>0160-2446</issn><issn>1533-4023</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1Us1u1DAQthBV2RYeAckHxC2tnTj-OUarApVWKkKFa-Q4k40hsYudbLW8DW9aZ3fZG76MPN_PaPwZIUzJDSVK3JJ0yoKxjColSJFu2dKir9CKlkWRMZIXr9GKUE6ynDH-Bl3F-DMRWCn4JbpUNC855yv0tzLzBFi7Fq_74J01-N7hH3bnU-1tYyfrHfYdrtzW-glctC5be7eDMFm3xXfuz34E3OzxVwjWtf4p2AFbh6ceEtj6VAc7j4cJVbsDNyVLvThudNgCrsKUhBAPhIew1S4u4CL_pps0_y266PQQ4d2pXqPvn-4e11-yzcPn-3W1yQwrGM1MQTUHxaGU0KomLZinBSnT0hhJu5wI1UIjtNGNFGAEM11LNDWKaWW4NMU1-nj0fQr-9wxxqkcbDQyDduDnWAupFKVSJKI8Ek3wMQbo6rTzqMO-pqRe0qn_pVOf0zm0aJK-P82YmxHas_AUR8I_nHAdjR66oJ2x8UzLeSmFkInGjrRnP6TXi7-G-RlC3YMepr7-398oXgD_kKkD</recordid><startdate>199703</startdate><enddate>199703</enddate><creator>Zhuo, Jialong</creator><creator>Casley, David</creator><creator>Murone, Carmel</creator><creator>Mendelsohn, Frederick A. 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O</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4341-c31a6e96e58ed9b912266614a8cc81f2079deb7acab87ec74cfd0a1c94a9c68c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Angiotensin I - blood</topic><topic>Angiotensin II - blood</topic><topic>Angiotensin-Converting Enzyme Inhibitors - pharmacology</topic><topic>Animals</topic><topic>Aorta - drug effects</topic><topic>Aorta - enzymology</topic><topic>Arteries - drug effects</topic><topic>Arteries - enzymology</topic><topic>Autoradiography</topic><topic>Biological and medical sciences</topic><topic>Blood Pressure - drug effects</topic><topic>Cardiovascular system</topic><topic>Carotid Arteries - drug effects</topic><topic>Carotid Arteries - enzymology</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - enzymology</topic><topic>Femoral Artery - drug effects</topic><topic>Femoral Artery - enzymology</topic><topic>Indoles - pharmacology</topic><topic>Kidney - enzymology</topic><topic>Lung - enzymology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>Myocardium - enzymology</topic><topic>Peptidyl-Dipeptidase A - blood</topic><topic>Peptidyl-Dipeptidase A - metabolism</topic><topic>Perindopril</topic><topic>Pharmacology. Drug treatments</topic><topic>Rabbits</topic><topic>Renin - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhuo, Jialong</creatorcontrib><creatorcontrib>Casley, David</creatorcontrib><creatorcontrib>Murone, Carmel</creatorcontrib><creatorcontrib>Mendelsohn, Frederick A. O</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cardiovascular pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhuo, Jialong</au><au>Casley, David</au><au>Murone, Carmel</au><au>Mendelsohn, Frederick A. O</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Acute and Chronic In Vivo Inhibition of Angiotensin-Converting Enzyme by Perindopril in the Endothelium and Adventitia of Large Arteries and Organs of the Rabbit</atitle><jtitle>Journal of cardiovascular pharmacology</jtitle><addtitle>J Cardiovasc Pharmacol</addtitle><date>1997-03</date><risdate>1997</risdate><volume>29</volume><issue>3</issue><spage>297</spage><epage>310</epage><pages>297-310</pages><issn>0160-2446</issn><eissn>1533-4023</eissn><coden>JCPCDT</coden><abstract>Angiotensin-converting enzyme (ACE) inhibitors are widely used in treating hypertension and chronic heart failure, but their precise sites and mechanisms of the actions are not completely understood. In this study, we evaluated the acute and chronic in vivo inhibition of ACE by perindopril in both the endothelium and adventitia of large blood vessels including the aorta, carotid, and femoral arteries, heart, lung, and kidney by using in vitro autoradiography with [I]351A as a ligand. After short-term (0.1, 0.3, and 1 mg/kg) or long-term oral admin-istration (0.3 mg/kg), perindopril significantly inhibited plasma ACE (p &lt; 0.001), the plasma angiotensin II (Ang II)/Ang I ratio (p &lt; 0.01), and decreased mean arterial pressure (p &lt; 0.001) in a dose-related manner. In the aorta, carotid, and femoral arteries, free ACE was inhibited to a similar extent in both the endthelium and adventitia by perindopril, in a dose-dependent manner, whereas total ACE in both layers of these vessels was unaltered. Similar short- and long-term ACE inhibition by perindopril was observed in the lung and heart, with somewhat greater inhibition of kidney and plasma ACE. Vascular and tissue ACE inhibition correlated highly with both plasma ACE and the plasma Ang II/Ang I ratio (r = 0.63-0.89; p &lt; 0.001). Whereas the effects of perindopril on blood pressure, plasma Ang II/Ang I ratio, plasma and vascular ACE were all highly dose dependent, there were no significant differences on the degree of ACE inhibition observed between the three large blood vessels or between their adventitial and endothelial layers. These results demonstrate that perindopril readily penetrates the vascular wall after short- or long-term oral administration, and in a dose-dependent manner, potently inhibits both endothelial and advential vascular ACE to a comparable degree. Therefore ACE inhibitors may be beneficial in inhibiting both circulating Ang II and its local formation in the vascular wall.</abstract><cop>Philadelphia, PA</cop><cop>Hagerstown, MD</cop><pub>Lippincott-Raven Publishers</pub><pmid>9125666</pmid><doi>10.1097/00005344-199703000-00001</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record>
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source MEDLINE; Journals@Ovid LWW Legacy Archive; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Ovid Autoload
subjects Angiotensin I - blood
Angiotensin II - blood
Angiotensin-Converting Enzyme Inhibitors - pharmacology
Animals
Aorta - drug effects
Aorta - enzymology
Arteries - drug effects
Arteries - enzymology
Autoradiography
Biological and medical sciences
Blood Pressure - drug effects
Cardiovascular system
Carotid Arteries - drug effects
Carotid Arteries - enzymology
Endothelium, Vascular - drug effects
Endothelium, Vascular - enzymology
Femoral Artery - drug effects
Femoral Artery - enzymology
Indoles - pharmacology
Kidney - enzymology
Lung - enzymology
Male
Medical sciences
Miscellaneous
Myocardium - enzymology
Peptidyl-Dipeptidase A - blood
Peptidyl-Dipeptidase A - metabolism
Perindopril
Pharmacology. Drug treatments
Rabbits
Renin - blood
title Acute and Chronic In Vivo Inhibition of Angiotensin-Converting Enzyme by Perindopril in the Endothelium and Adventitia of Large Arteries and Organs of the Rabbit
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