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 |
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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. |
doi_str_mv | 10.1097/00005344-199703000-00001 |
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O</creator><creatorcontrib>Zhuo, Jialong ; Casley, David ; Murone, Carmel ; Mendelsohn, Frederick A. O</creatorcontrib><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.</description><identifier>ISSN: 0160-2446</identifier><identifier>EISSN: 1533-4023</identifier><identifier>DOI: 10.1097/00005344-199703000-00001</identifier><identifier>PMID: 9125666</identifier><identifier>CODEN: JCPCDT</identifier><language>eng</language><publisher>Philadelphia, PA: Lippincott-Raven Publishers</publisher><subject>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</subject><ispartof>Journal of cardiovascular pharmacology, 1997-03, Vol.29 (3), p.297-310</ispartof><rights>Lippincott-Raven Publishers</rights><rights>1997 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4341-c31a6e96e58ed9b912266614a8cc81f2079deb7acab87ec74cfd0a1c94a9c68c3</citedby><cites>FETCH-LOGICAL-c4341-c31a6e96e58ed9b912266614a8cc81f2079deb7acab87ec74cfd0a1c94a9c68c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf><![CDATA[$$Uhttp://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&PDF=y&D=ovft&AN=00005344-199703000-00001$$EPDF$$P50$$Gwolterskluwer$$H]]></linktopdf><linktohtml>$$Uhttp://ovidsp.ovid.com/ovidweb.cgi?T=JS&NEWS=n&CSC=Y&PAGE=fulltext&D=ovft&AN=00005344-199703000-00001$$EHTML$$P50$$Gwolterskluwer$$H</linktohtml><link.rule.ids>314,780,784,4609,27924,27925,64666,65461</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2658778$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9125666$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhuo, Jialong</creatorcontrib><creatorcontrib>Casley, David</creatorcontrib><creatorcontrib>Murone, Carmel</creatorcontrib><creatorcontrib>Mendelsohn, Frederick A. 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 < 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.</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. O</creator><general>Lippincott-Raven Publishers</general><general>Lippincott</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>199703</creationdate><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><author>Zhuo, Jialong ; Casley, David ; Murone, Carmel ; Mendelsohn, Frederick A. 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 < 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.</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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