Protective Effects of Imidapril on He-Ne Laser-Induced Thrombosis in Cerebral Blood Vessels of Stroke-Prone Spontaneously Hypertensive Rats
Summary Inhibitors of angiotensin converting enzyme (ACE) have been developed recently for therapeutic purposes in hypertension and ischemic cardiovascular diseases. Ogiku et al. (1) reported that one such inhibitor, imidapril, significantly prolonged survival in stroke-prone spontaneously hypertens...
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| creator | Sasaki, Yasuto Noguchi, Takanori Seki, Junji Giddings, J. C. Yamamoto, Junichiro |
| description | Summary
Inhibitors of angiotensin converting enzyme (ACE) have been developed recently for therapeutic purposes in hypertension and ischemic cardiovascular diseases. Ogiku et al. (1) reported that one such inhibitor, imidapril, significantly prolonged survival in stroke-prone spontaneously hypertensive rats (SHRSP). The present study was designed to investigate the effect of imidapril on cerebral blood vessels in SHRSP to clarify role of the ACE inhibitor in mechanisms of cerebral thrombosis and stroke. Imidapril was administered orally at 1.0 and 5.0 mg/kg/day for 3 weeks from the age of 7 weeks, and was shown to prevent the usual increase in blood pressure seen in these animals. It also delayed He-Ne laser-induced cerebral thrombosis and increased significantly the plasma concentration of nitric oxide metabolites (NO
2
/NO
3
). To confirm the association between nitric oxide (NO) and these effects of imidapril, an inhibitor of nitric oxide synthase,
N
G
- nitro-L-arginine methyl ester hydrochloride (L-NAME) was dissolved in drinking water and administered to the animals for 3 weeks. Four of six rats died from stroke when L-NAME was given alone. When imidapril (5.0 mg/kg/day) was administered with L-NAME, however, the animals showed no signs or symptoms of stroke. In these instances, therefore, the concurrent administration of L-NAME with imidapril reversed significantly the effects of imidapril. Intravenous injection of imidaprilat (100 µg/kg), an active metabolite of imidapril, also decreased blood pressure significantly and increased the plasma levels of NO
2
/NO
3
after 5 min. Moreover, imidaprilat enlarged arteriolar diameters and caused an increase in red cell velocity and mean blood flow in pial arterioles after 15 min.
The results strongly suggested that imidapril protects cerebral vessels in SHRSP by elevating the release of NO, thereby improving the cerebral circulation and reducing the tendency to thrombosis and stroke. |
| doi_str_mv | 10.1055/s-0037-1613899 |
| format | Article |
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Inhibitors of angiotensin converting enzyme (ACE) have been developed recently for therapeutic purposes in hypertension and ischemic cardiovascular diseases. Ogiku et al. (1) reported that one such inhibitor, imidapril, significantly prolonged survival in stroke-prone spontaneously hypertensive rats (SHRSP). The present study was designed to investigate the effect of imidapril on cerebral blood vessels in SHRSP to clarify role of the ACE inhibitor in mechanisms of cerebral thrombosis and stroke. Imidapril was administered orally at 1.0 and 5.0 mg/kg/day for 3 weeks from the age of 7 weeks, and was shown to prevent the usual increase in blood pressure seen in these animals. It also delayed He-Ne laser-induced cerebral thrombosis and increased significantly the plasma concentration of nitric oxide metabolites (NO
2
/NO
3
). To confirm the association between nitric oxide (NO) and these effects of imidapril, an inhibitor of nitric oxide synthase,
N
G
- nitro-L-arginine methyl ester hydrochloride (L-NAME) was dissolved in drinking water and administered to the animals for 3 weeks. Four of six rats died from stroke when L-NAME was given alone. When imidapril (5.0 mg/kg/day) was administered with L-NAME, however, the animals showed no signs or symptoms of stroke. In these instances, therefore, the concurrent administration of L-NAME with imidapril reversed significantly the effects of imidapril. Intravenous injection of imidaprilat (100 µg/kg), an active metabolite of imidapril, also decreased blood pressure significantly and increased the plasma levels of NO
2
/NO
3
after 5 min. Moreover, imidaprilat enlarged arteriolar diameters and caused an increase in red cell velocity and mean blood flow in pial arterioles after 15 min.
The results strongly suggested that imidapril protects cerebral vessels in SHRSP by elevating the release of NO, thereby improving the cerebral circulation and reducing the tendency to thrombosis and stroke.</description><identifier>ISSN: 0340-6245</identifier><identifier>EISSN: 2567-689X</identifier><identifier>DOI: 10.1055/s-0037-1613899</identifier><identifier>PMID: 10823269</identifier><identifier>CODEN: THHADQ</identifier><language>eng</language><publisher>Stuttgart: Schattauer Verlag für Medizin und Naturwissenschaften</publisher><subject>Angiotensin-Converting Enzyme Inhibitors - pharmacology ; Angiotensin-Converting Enzyme Inhibitors - therapeutic use ; Animals ; Antihypertensive agents ; Antihypertensive Agents - pharmacology ; Antihypertensive Agents - therapeutic use ; Arterioles - ultrastructure ; Biological and medical sciences ; Blood. Blood coagulation. Reticuloendothelial system ; Cardiovascular system ; Cerebral Arteries - ultrastructure ; Drug Evaluation, Preclinical ; Female ; Genetic Predisposition to Disease ; Hemorheology - drug effects ; Hypertension - genetics ; Hypertension - prevention & control ; Imidazoles - antagonists & inhibitors ; Imidazoles - pharmacology ; Imidazoles - therapeutic use ; Imidazolidines ; Intracranial Thrombosis - drug therapy ; Intracranial Thrombosis - genetics ; Intracranial Thrombosis - prevention & control ; Lasers - adverse effects ; Male ; Medical sciences ; Microcirculation - drug effects ; NG-Nitroarginine Methyl Ester - toxicity ; Nitric Oxide - physiology ; Nitric Oxide Synthase - antagonists & inhibitors ; Pharmacology. Drug treatments ; Rats ; Rats, Inbred SHR ; Review Article</subject><ispartof>Thrombosis and haemostasis, 2000-05, Vol.83 (5), p.722-727</ispartof><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c548t-9df9092884f74bd1d6621eaa650643a65cf260e1f719524b6b1fb634d705e7653</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.thieme-connect.de/products/ejournals/pdf/10.1055/s-0037-1613899.pdf$$EPDF$$P50$$Gthieme$$H</linktopdf><linktohtml>$$Uhttps://www.thieme-connect.de/products/ejournals/html/10.1055/s-0037-1613899$$EHTML$$P50$$Gthieme$$H</linktohtml><link.rule.ids>314,777,781,3004,3005,27905,27906,54540,54541</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1366996$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10823269$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sasaki, Yasuto</creatorcontrib><creatorcontrib>Noguchi, Takanori</creatorcontrib><creatorcontrib>Seki, Junji</creatorcontrib><creatorcontrib>Giddings, J. C.</creatorcontrib><creatorcontrib>Yamamoto, Junichiro</creatorcontrib><title>Protective Effects of Imidapril on He-Ne Laser-Induced Thrombosis in Cerebral Blood Vessels of Stroke-Prone Spontaneously Hypertensive Rats</title><title>Thrombosis and haemostasis</title><addtitle>Thromb Haemost</addtitle><description>Summary
Inhibitors of angiotensin converting enzyme (ACE) have been developed recently for therapeutic purposes in hypertension and ischemic cardiovascular diseases. Ogiku et al. (1) reported that one such inhibitor, imidapril, significantly prolonged survival in stroke-prone spontaneously hypertensive rats (SHRSP). The present study was designed to investigate the effect of imidapril on cerebral blood vessels in SHRSP to clarify role of the ACE inhibitor in mechanisms of cerebral thrombosis and stroke. Imidapril was administered orally at 1.0 and 5.0 mg/kg/day for 3 weeks from the age of 7 weeks, and was shown to prevent the usual increase in blood pressure seen in these animals. It also delayed He-Ne laser-induced cerebral thrombosis and increased significantly the plasma concentration of nitric oxide metabolites (NO
2
/NO
3
). To confirm the association between nitric oxide (NO) and these effects of imidapril, an inhibitor of nitric oxide synthase,
N
G
- nitro-L-arginine methyl ester hydrochloride (L-NAME) was dissolved in drinking water and administered to the animals for 3 weeks. Four of six rats died from stroke when L-NAME was given alone. When imidapril (5.0 mg/kg/day) was administered with L-NAME, however, the animals showed no signs or symptoms of stroke. In these instances, therefore, the concurrent administration of L-NAME with imidapril reversed significantly the effects of imidapril. Intravenous injection of imidaprilat (100 µg/kg), an active metabolite of imidapril, also decreased blood pressure significantly and increased the plasma levels of NO
2
/NO
3
after 5 min. Moreover, imidaprilat enlarged arteriolar diameters and caused an increase in red cell velocity and mean blood flow in pial arterioles after 15 min.
The results strongly suggested that imidapril protects cerebral vessels in SHRSP by elevating the release of NO, thereby improving the cerebral circulation and reducing the tendency to thrombosis and stroke.</description><subject>Angiotensin-Converting Enzyme Inhibitors - pharmacology</subject><subject>Angiotensin-Converting Enzyme Inhibitors - therapeutic use</subject><subject>Animals</subject><subject>Antihypertensive agents</subject><subject>Antihypertensive Agents - pharmacology</subject><subject>Antihypertensive Agents - therapeutic use</subject><subject>Arterioles - ultrastructure</subject><subject>Biological and medical sciences</subject><subject>Blood. Blood coagulation. Reticuloendothelial system</subject><subject>Cardiovascular system</subject><subject>Cerebral Arteries - ultrastructure</subject><subject>Drug Evaluation, Preclinical</subject><subject>Female</subject><subject>Genetic Predisposition to Disease</subject><subject>Hemorheology - drug effects</subject><subject>Hypertension - genetics</subject><subject>Hypertension - prevention & control</subject><subject>Imidazoles - antagonists & inhibitors</subject><subject>Imidazoles - pharmacology</subject><subject>Imidazoles - therapeutic use</subject><subject>Imidazolidines</subject><subject>Intracranial Thrombosis - drug therapy</subject><subject>Intracranial Thrombosis - genetics</subject><subject>Intracranial Thrombosis - prevention & control</subject><subject>Lasers - adverse effects</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microcirculation - drug effects</subject><subject>NG-Nitroarginine Methyl Ester - toxicity</subject><subject>Nitric Oxide - physiology</subject><subject>Nitric Oxide Synthase - antagonists & inhibitors</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Inbred SHR</subject><subject>Review Article</subject><issn>0340-6245</issn><issn>2567-689X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqtkUFv1DAQhSMEokvhyhH5wDXFThwnPsKqsCutCqIFcbMcZ6ykJHbkcYr2N_Cn8bKrFiFx4zS25pv3NG-y7CWjF4xW1RvMKS3rnAlWNlI-ylZFJepcNPLb42xFS05zUfDqLHuGeEspE1xWT7MzRpuiLIRcZT8_BR_BxOEOyKW16YXEW7Kdhk7PYRiJd2QD-RWQnUYI-dZ1i4GO3PTBT63HAcngyBoCtEGP5N3ofUe-AiKMv4WuY_DfIU8uDsj17F3UDvyC455s9jOECA4P3p91xOfZE6tHhBenep59eX95s97ku48ftuu3u9xUvIm57KyksmgabmvedqwTomCgtaio4GUqxhaCArM1k1XBW9Ey24qSdzWtoBZVeZ5dHHVN8IgBrEqbTjrsFaPqkKpCdUhVnVJNA6-OA_PSTtD9gR9jTMDrE6DR6NEG7cyAD1wphJQiYfkRi_0AE6hbvwSXNv23rznyaHodo14g3GvG-wMo7TrVa5g8Rn34m5QyuJgawfQpXDUgLqBwBjPoUU3aLWjCMEdV8IInl-E_uqSz_O2gsPc_VB-nsfwFGnbgEw</recordid><startdate>20000501</startdate><enddate>20000501</enddate><creator>Sasaki, Yasuto</creator><creator>Noguchi, Takanori</creator><creator>Seki, Junji</creator><creator>Giddings, J. C.</creator><creator>Yamamoto, Junichiro</creator><general>Schattauer Verlag für Medizin und Naturwissenschaften</general><general>Schattauer GmbH</general><general>Schattauer</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></search><sort><creationdate>20000501</creationdate><title>Protective Effects of Imidapril on He-Ne Laser-Induced Thrombosis in Cerebral Blood Vessels of Stroke-Prone Spontaneously Hypertensive Rats</title><author>Sasaki, Yasuto ; Noguchi, Takanori ; Seki, Junji ; Giddings, J. C. ; Yamamoto, Junichiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c548t-9df9092884f74bd1d6621eaa650643a65cf260e1f719524b6b1fb634d705e7653</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Angiotensin-Converting Enzyme Inhibitors - pharmacology</topic><topic>Angiotensin-Converting Enzyme Inhibitors - therapeutic use</topic><topic>Animals</topic><topic>Antihypertensive agents</topic><topic>Antihypertensive Agents - pharmacology</topic><topic>Antihypertensive Agents - therapeutic use</topic><topic>Arterioles - ultrastructure</topic><topic>Biological and medical sciences</topic><topic>Blood. Blood coagulation. Reticuloendothelial system</topic><topic>Cardiovascular system</topic><topic>Cerebral Arteries - ultrastructure</topic><topic>Drug Evaluation, Preclinical</topic><topic>Female</topic><topic>Genetic Predisposition to Disease</topic><topic>Hemorheology - drug effects</topic><topic>Hypertension - genetics</topic><topic>Hypertension - prevention & control</topic><topic>Imidazoles - antagonists & inhibitors</topic><topic>Imidazoles - pharmacology</topic><topic>Imidazoles - therapeutic use</topic><topic>Imidazolidines</topic><topic>Intracranial Thrombosis - drug therapy</topic><topic>Intracranial Thrombosis - genetics</topic><topic>Intracranial Thrombosis - prevention & control</topic><topic>Lasers - adverse effects</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microcirculation - drug effects</topic><topic>NG-Nitroarginine Methyl Ester - toxicity</topic><topic>Nitric Oxide - physiology</topic><topic>Nitric Oxide Synthase - antagonists & inhibitors</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Rats, Inbred SHR</topic><topic>Review Article</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sasaki, Yasuto</creatorcontrib><creatorcontrib>Noguchi, Takanori</creatorcontrib><creatorcontrib>Seki, Junji</creatorcontrib><creatorcontrib>Giddings, J. C.</creatorcontrib><creatorcontrib>Yamamoto, Junichiro</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><jtitle>Thrombosis and haemostasis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sasaki, Yasuto</au><au>Noguchi, Takanori</au><au>Seki, Junji</au><au>Giddings, J. C.</au><au>Yamamoto, Junichiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protective Effects of Imidapril on He-Ne Laser-Induced Thrombosis in Cerebral Blood Vessels of Stroke-Prone Spontaneously Hypertensive Rats</atitle><jtitle>Thrombosis and haemostasis</jtitle><addtitle>Thromb Haemost</addtitle><date>2000-05-01</date><risdate>2000</risdate><volume>83</volume><issue>5</issue><spage>722</spage><epage>727</epage><pages>722-727</pages><issn>0340-6245</issn><eissn>2567-689X</eissn><coden>THHADQ</coden><abstract>Summary
Inhibitors of angiotensin converting enzyme (ACE) have been developed recently for therapeutic purposes in hypertension and ischemic cardiovascular diseases. Ogiku et al. (1) reported that one such inhibitor, imidapril, significantly prolonged survival in stroke-prone spontaneously hypertensive rats (SHRSP). The present study was designed to investigate the effect of imidapril on cerebral blood vessels in SHRSP to clarify role of the ACE inhibitor in mechanisms of cerebral thrombosis and stroke. Imidapril was administered orally at 1.0 and 5.0 mg/kg/day for 3 weeks from the age of 7 weeks, and was shown to prevent the usual increase in blood pressure seen in these animals. It also delayed He-Ne laser-induced cerebral thrombosis and increased significantly the plasma concentration of nitric oxide metabolites (NO
2
/NO
3
). To confirm the association between nitric oxide (NO) and these effects of imidapril, an inhibitor of nitric oxide synthase,
N
G
- nitro-L-arginine methyl ester hydrochloride (L-NAME) was dissolved in drinking water and administered to the animals for 3 weeks. Four of six rats died from stroke when L-NAME was given alone. When imidapril (5.0 mg/kg/day) was administered with L-NAME, however, the animals showed no signs or symptoms of stroke. In these instances, therefore, the concurrent administration of L-NAME with imidapril reversed significantly the effects of imidapril. Intravenous injection of imidaprilat (100 µg/kg), an active metabolite of imidapril, also decreased blood pressure significantly and increased the plasma levels of NO
2
/NO
3
after 5 min. Moreover, imidaprilat enlarged arteriolar diameters and caused an increase in red cell velocity and mean blood flow in pial arterioles after 15 min.
The results strongly suggested that imidapril protects cerebral vessels in SHRSP by elevating the release of NO, thereby improving the cerebral circulation and reducing the tendency to thrombosis and stroke.</abstract><cop>Stuttgart</cop><pub>Schattauer Verlag für Medizin und Naturwissenschaften</pub><pmid>10823269</pmid><doi>10.1055/s-0037-1613899</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0340-6245 |
| ispartof | Thrombosis and haemostasis, 2000-05, Vol.83 (5), p.722-727 |
| issn | 0340-6245 2567-689X |
| language | eng |
| recordid | cdi_thieme_journals_10_1055_s_0037_1613899 |
| source | MEDLINE; Thieme Connect Journals |
| subjects | Angiotensin-Converting Enzyme Inhibitors - pharmacology Angiotensin-Converting Enzyme Inhibitors - therapeutic use Animals Antihypertensive agents Antihypertensive Agents - pharmacology Antihypertensive Agents - therapeutic use Arterioles - ultrastructure Biological and medical sciences Blood. Blood coagulation. Reticuloendothelial system Cardiovascular system Cerebral Arteries - ultrastructure Drug Evaluation, Preclinical Female Genetic Predisposition to Disease Hemorheology - drug effects Hypertension - genetics Hypertension - prevention & control Imidazoles - antagonists & inhibitors Imidazoles - pharmacology Imidazoles - therapeutic use Imidazolidines Intracranial Thrombosis - drug therapy Intracranial Thrombosis - genetics Intracranial Thrombosis - prevention & control Lasers - adverse effects Male Medical sciences Microcirculation - drug effects NG-Nitroarginine Methyl Ester - toxicity Nitric Oxide - physiology Nitric Oxide Synthase - antagonists & inhibitors Pharmacology. Drug treatments Rats Rats, Inbred SHR Review Article |
| title | Protective Effects of Imidapril on He-Ne Laser-Induced Thrombosis in Cerebral Blood Vessels of Stroke-Prone Spontaneously Hypertensive Rats |
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