Stereoselective inhibition of thromboxane-induced coronary vasoconstriction by 1,4-dihydropyridine calcium channel antagonists
The biological activity of the (+)‐S‐ and (−)‐R‐enantiomers of niguldipine, of the (−)‐S‐ and (+)‐R‐enantiomers of felodipine and nitrendipine, and of rac‐nisoldipine and rac‐nimodipine was investigated in vitro and in vivo. Inhibition of coronary vasoconstriction due to the thromboxane A2 (TxA2)‐mi...
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| Veröffentlicht in: | Chirality (New York, N.Y.) N.Y.), 1990, Vol.2 (4), p.233-240 |
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| creator | Eltze, Manfrid Sanders, Karl H. Boss, Hildegard Boer, Rainer Ulrich, Wolf-Rüdiger Flockerzi, Dieter |
| description | The biological activity of the (+)‐S‐ and (−)‐R‐enantiomers of niguldipine, of the (−)‐S‐ and (+)‐R‐enantiomers of felodipine and nitrendipine, and of rac‐nisoldipine and rac‐nimodipine was investigated in vitro and in vivo. Inhibition of coronary vasoconstriction due to the thromboxane A2 (TxA2)‐mimetic U‐46619 in guinea pig Langendorff hearts, displacement of (+)‐[3H]isradipine from calcium channel binding sites of guinea pig skeletal muscle T‐tubule membranes, and blood pressure reduction in spontaneously hypertensive rats were determined. The enantiomers were obtained by stereoselective synthesis. Cross‐contamination was |
| doi_str_mv | 10.1002/chir.530020408 |
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Inhibition of coronary vasoconstriction due to the thromboxane A2 (TxA2)‐mimetic U‐46619 in guinea pig Langendorff hearts, displacement of (+)‐[3H]isradipine from calcium channel binding sites of guinea pig skeletal muscle T‐tubule membranes, and blood pressure reduction in spontaneously hypertensive rats were determined. The enantiomers were obtained by stereoselective synthesis. Cross‐contamination was <0.5% for both S‐ and R‐enantiomers of niguldipine and nitrendipine and <1% for those of felodipine. From the doses necessary for a 50% inhibition of coronary vasoconstriction, stereoselectivity ratios for (+)‐(S)‐/(−)‐(R)‐niguldipine, (−)‐(S)‐/(+)‐(R)‐felodipine, and (−)‐(S)‐/(+)‐(R)‐nitrendipine of 28, 13, and 7, respectively, were calculated. The potency ratio racnisoldipine/rac‐nimodipine was 3.5. Ratios obtained from binding experiments and antihypertensive activity were (+)‐(S)‐/(−)‐(R)‐niguldipine = 45 and 35, (−)‐(S)‐/(+)‐(R)‐felodipine = 12 and 13, (−)‐(S)‐/(+)‐(R)‐nitrendipine = 8 and 8, and rac‐nisoldipine/rac‐nimodipine = 8 and 7, respectively. Highly significant correlations were found between the in vitro potency of the substances to prevent U‐46619‐induced coronary vasoconstriction and their affinity for calcium channel binding sites as well as their antihypertensive activity. The mechanism of TxA2‐induced coronary vasoconstriction in guinea pig Langendorff hearts can be readily explained by a transmembrane influx of extracellular Ca2+ susceptible to stereoselective blockade by 1,4‐dihydropyridine calcium channel antagonists.</description><identifier>ISSN: 0899-0042</identifier><identifier>EISSN: 1520-636X</identifier><identifier>DOI: 10.1002/chir.530020408</identifier><identifier>PMID: 1964575</identifier><language>eng</language><publisher>New York: Alan R. Liss, Inc</publisher><subject>1,4‐dihydropypyridine enantiomers ; 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid ; 4-dihydropypyridine enantiomers ; 550201 - Biochemistry- Tracer Techniques ; ANIMALS ; ARTERIES ; AZINES ; BASIC BIOLOGICAL SCIENCES ; Binding, Competitive ; BIOCHEMICAL REACTION KINETICS ; BLOOD PRESSURE ; BLOOD VESSELS ; BODY ; calcium channel binding ; Calcium Channel Blockers - pharmacology ; Calcium Channels - drug effects ; Calcium Channels - metabolism ; CARDIOVASCULAR DISEASES ; CARDIOVASCULAR SYSTEM ; CELL CONSTITUENTS ; Cell Membrane - metabolism ; CELL MEMBRANES ; CORONARIES ; coronary vasoconstriction ; Dihydropyridines - metabolism ; Dihydropyridines - pharmacology ; DISEASES ; GUINEA PIGS ; HEART ; Heart - drug effects ; Heart - physiology ; HETEROCYCLIC COMPOUNDS ; HYDROGEN COMPOUNDS ; HYPERTENSION ; IN VITRO ; In Vitro Techniques ; IN VIVO ; INHIBITION ; ISOTOPE APPLICATIONS ; Isradipine ; KINETICS ; Male ; MAMMALS ; MEMBRANE PROTEINS ; MEMBRANES ; MUSCLES ; Muscles - metabolism ; ORGANIC COMPOUNDS ; ORGANIC NITROGEN COMPOUNDS ; ORGANS ; PORINS ; Prostaglandin Endoperoxides, Synthetic - pharmacology ; PROSTAGLANDINS ; PROTEINS ; PYRIDINES ; Pyridines - metabolism ; Radioligand Assay ; RATS ; Rats, Inbred SHR ; REACTION KINETICS ; RECEPTORS ; RODENTS ; Stereoisomerism ; stereoselectivity ; Structure-Activity Relationship ; STRUCTURE-ACTIVITY RELATIONSHIPS ; SYMPTOMS ; thromboxane A2 (TxA2) ; Thromboxane A2 - physiology ; TRACER TECHNIQUES ; Tritium ; TRITIUM COMPOUNDS ; VASCULAR DISEASES ; VASOCONSTRICTION ; Vasoconstriction - drug effects ; VERTEBRATES</subject><ispartof>Chirality (New York, N.Y.), 1990, Vol.2 (4), p.233-240</ispartof><rights>Copyright © 1990 Wiley‐Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4058-2030c8cfd7590a2ca45c24ca2a4a884f3c204914f3a95588dc333ef809c0b9c23</citedby><cites>FETCH-LOGICAL-c4058-2030c8cfd7590a2ca45c24ca2a4a884f3c204914f3a95588dc333ef809c0b9c23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fchir.530020408$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fchir.530020408$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,4010,27900,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1964575$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/5583743$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Eltze, Manfrid</creatorcontrib><creatorcontrib>Sanders, Karl H.</creatorcontrib><creatorcontrib>Boss, Hildegard</creatorcontrib><creatorcontrib>Boer, Rainer</creatorcontrib><creatorcontrib>Ulrich, Wolf-Rüdiger</creatorcontrib><creatorcontrib>Flockerzi, Dieter</creatorcontrib><title>Stereoselective inhibition of thromboxane-induced coronary vasoconstriction by 1,4-dihydropyridine calcium channel antagonists</title><title>Chirality (New York, N.Y.)</title><addtitle>Chirality</addtitle><description>The biological activity of the (+)‐S‐ and (−)‐R‐enantiomers of niguldipine, of the (−)‐S‐ and (+)‐R‐enantiomers of felodipine and nitrendipine, and of rac‐nisoldipine and rac‐nimodipine was investigated in vitro and in vivo. Inhibition of coronary vasoconstriction due to the thromboxane A2 (TxA2)‐mimetic U‐46619 in guinea pig Langendorff hearts, displacement of (+)‐[3H]isradipine from calcium channel binding sites of guinea pig skeletal muscle T‐tubule membranes, and blood pressure reduction in spontaneously hypertensive rats were determined. The enantiomers were obtained by stereoselective synthesis. Cross‐contamination was <0.5% for both S‐ and R‐enantiomers of niguldipine and nitrendipine and <1% for those of felodipine. From the doses necessary for a 50% inhibition of coronary vasoconstriction, stereoselectivity ratios for (+)‐(S)‐/(−)‐(R)‐niguldipine, (−)‐(S)‐/(+)‐(R)‐felodipine, and (−)‐(S)‐/(+)‐(R)‐nitrendipine of 28, 13, and 7, respectively, were calculated. The potency ratio racnisoldipine/rac‐nimodipine was 3.5. Ratios obtained from binding experiments and antihypertensive activity were (+)‐(S)‐/(−)‐(R)‐niguldipine = 45 and 35, (−)‐(S)‐/(+)‐(R)‐felodipine = 12 and 13, (−)‐(S)‐/(+)‐(R)‐nitrendipine = 8 and 8, and rac‐nisoldipine/rac‐nimodipine = 8 and 7, respectively. Highly significant correlations were found between the in vitro potency of the substances to prevent U‐46619‐induced coronary vasoconstriction and their affinity for calcium channel binding sites as well as their antihypertensive activity. The mechanism of TxA2‐induced coronary vasoconstriction in guinea pig Langendorff hearts can be readily explained by a transmembrane influx of extracellular Ca2+ susceptible to stereoselective blockade by 1,4‐dihydropyridine calcium channel antagonists.</description><subject>1,4‐dihydropypyridine enantiomers</subject><subject>15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid</subject><subject>4-dihydropypyridine enantiomers</subject><subject>550201 - Biochemistry- Tracer Techniques</subject><subject>ANIMALS</subject><subject>ARTERIES</subject><subject>AZINES</subject><subject>BASIC BIOLOGICAL SCIENCES</subject><subject>Binding, Competitive</subject><subject>BIOCHEMICAL REACTION KINETICS</subject><subject>BLOOD PRESSURE</subject><subject>BLOOD VESSELS</subject><subject>BODY</subject><subject>calcium channel binding</subject><subject>Calcium Channel Blockers - pharmacology</subject><subject>Calcium Channels - drug effects</subject><subject>Calcium Channels - metabolism</subject><subject>CARDIOVASCULAR DISEASES</subject><subject>CARDIOVASCULAR SYSTEM</subject><subject>CELL CONSTITUENTS</subject><subject>Cell Membrane - metabolism</subject><subject>CELL MEMBRANES</subject><subject>CORONARIES</subject><subject>coronary vasoconstriction</subject><subject>Dihydropyridines - metabolism</subject><subject>Dihydropyridines - pharmacology</subject><subject>DISEASES</subject><subject>GUINEA PIGS</subject><subject>HEART</subject><subject>Heart - drug effects</subject><subject>Heart - physiology</subject><subject>HETEROCYCLIC COMPOUNDS</subject><subject>HYDROGEN COMPOUNDS</subject><subject>HYPERTENSION</subject><subject>IN VITRO</subject><subject>In Vitro Techniques</subject><subject>IN VIVO</subject><subject>INHIBITION</subject><subject>ISOTOPE APPLICATIONS</subject><subject>Isradipine</subject><subject>KINETICS</subject><subject>Male</subject><subject>MAMMALS</subject><subject>MEMBRANE PROTEINS</subject><subject>MEMBRANES</subject><subject>MUSCLES</subject><subject>Muscles - metabolism</subject><subject>ORGANIC COMPOUNDS</subject><subject>ORGANIC NITROGEN COMPOUNDS</subject><subject>ORGANS</subject><subject>PORINS</subject><subject>Prostaglandin Endoperoxides, Synthetic - pharmacology</subject><subject>PROSTAGLANDINS</subject><subject>PROTEINS</subject><subject>PYRIDINES</subject><subject>Pyridines - metabolism</subject><subject>Radioligand Assay</subject><subject>RATS</subject><subject>Rats, Inbred SHR</subject><subject>REACTION KINETICS</subject><subject>RECEPTORS</subject><subject>RODENTS</subject><subject>Stereoisomerism</subject><subject>stereoselectivity</subject><subject>Structure-Activity Relationship</subject><subject>STRUCTURE-ACTIVITY RELATIONSHIPS</subject><subject>SYMPTOMS</subject><subject>thromboxane A2 (TxA2)</subject><subject>Thromboxane A2 - physiology</subject><subject>TRACER TECHNIQUES</subject><subject>Tritium</subject><subject>TRITIUM COMPOUNDS</subject><subject>VASCULAR DISEASES</subject><subject>VASOCONSTRICTION</subject><subject>Vasoconstriction - drug effects</subject><subject>VERTEBRATES</subject><issn>0899-0042</issn><issn>1520-636X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUU1v1DAUtBCobAtXbkgRB07N1ontxD6i7SeqWrGAQFws58UhhsRebKc0F347LqkKN07vSW9m9GYGoRcFXhcYl0fQG79mJK2YYv4IrQpW4rwi1efHaIW5EDnGtHyK9kP4hjEWFaF7aK8QFWU1W6Ff76P22gU9aIjmRmfG9qYx0TibuS6LvXdj426V1bmx7QS6zcB5Z5WfsxsVHDgbojfwh9DMWXFI89b0c-vdbvamNVZnoAYw05hBr6zVQ6ZsVF-dNSGGZ-hJp4agn9_PA_Tx9OTD5jy_vD672Ly5zIFixvMSEwwcurZmAqsSFGVQUlCloopz2hFI7kWRFiUY47wFQojuOBaAGwElOUCvFl0XopEBTNTQp99tci0Tg9SUJNDrBbTz7sekQ5SjCaCHIbl3U5A8fcFoVSTgegGCdyF43cmdN2OKRBZY3rUi71qRD60kwst75akZdfsXvtSQ7mK5_zSDnv-jJjfnF9t_tfOFm_LUtw9c5b_LqiY1k5-uzuT27Zcrfky38h35De26q3E</recordid><startdate>1990</startdate><enddate>1990</enddate><creator>Eltze, Manfrid</creator><creator>Sanders, Karl H.</creator><creator>Boss, Hildegard</creator><creator>Boer, Rainer</creator><creator>Ulrich, Wolf-Rüdiger</creator><creator>Flockerzi, Dieter</creator><general>Alan R. Liss, Inc</general><scope>BSCLL</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><scope>OTOTI</scope></search><sort><creationdate>1990</creationdate><title>Stereoselective inhibition of thromboxane-induced coronary vasoconstriction by 1,4-dihydropyridine calcium channel antagonists</title><author>Eltze, Manfrid ; Sanders, Karl H. ; Boss, Hildegard ; Boer, Rainer ; Ulrich, Wolf-Rüdiger ; Flockerzi, Dieter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4058-2030c8cfd7590a2ca45c24ca2a4a884f3c204914f3a95588dc333ef809c0b9c23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1990</creationdate><topic>1,4‐dihydropypyridine enantiomers</topic><topic>15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid</topic><topic>4-dihydropypyridine enantiomers</topic><topic>550201 - Biochemistry- Tracer Techniques</topic><topic>ANIMALS</topic><topic>ARTERIES</topic><topic>AZINES</topic><topic>BASIC BIOLOGICAL SCIENCES</topic><topic>Binding, Competitive</topic><topic>BIOCHEMICAL REACTION KINETICS</topic><topic>BLOOD PRESSURE</topic><topic>BLOOD VESSELS</topic><topic>BODY</topic><topic>calcium channel binding</topic><topic>Calcium Channel Blockers - pharmacology</topic><topic>Calcium Channels - drug effects</topic><topic>Calcium Channels - metabolism</topic><topic>CARDIOVASCULAR DISEASES</topic><topic>CARDIOVASCULAR SYSTEM</topic><topic>CELL CONSTITUENTS</topic><topic>Cell Membrane - metabolism</topic><topic>CELL MEMBRANES</topic><topic>CORONARIES</topic><topic>coronary vasoconstriction</topic><topic>Dihydropyridines - metabolism</topic><topic>Dihydropyridines - pharmacology</topic><topic>DISEASES</topic><topic>GUINEA PIGS</topic><topic>HEART</topic><topic>Heart - drug effects</topic><topic>Heart - physiology</topic><topic>HETEROCYCLIC COMPOUNDS</topic><topic>HYDROGEN COMPOUNDS</topic><topic>HYPERTENSION</topic><topic>IN VITRO</topic><topic>In Vitro Techniques</topic><topic>IN VIVO</topic><topic>INHIBITION</topic><topic>ISOTOPE APPLICATIONS</topic><topic>Isradipine</topic><topic>KINETICS</topic><topic>Male</topic><topic>MAMMALS</topic><topic>MEMBRANE PROTEINS</topic><topic>MEMBRANES</topic><topic>MUSCLES</topic><topic>Muscles - metabolism</topic><topic>ORGANIC COMPOUNDS</topic><topic>ORGANIC NITROGEN COMPOUNDS</topic><topic>ORGANS</topic><topic>PORINS</topic><topic>Prostaglandin Endoperoxides, Synthetic - pharmacology</topic><topic>PROSTAGLANDINS</topic><topic>PROTEINS</topic><topic>PYRIDINES</topic><topic>Pyridines - metabolism</topic><topic>Radioligand Assay</topic><topic>RATS</topic><topic>Rats, Inbred SHR</topic><topic>REACTION KINETICS</topic><topic>RECEPTORS</topic><topic>RODENTS</topic><topic>Stereoisomerism</topic><topic>stereoselectivity</topic><topic>Structure-Activity Relationship</topic><topic>STRUCTURE-ACTIVITY RELATIONSHIPS</topic><topic>SYMPTOMS</topic><topic>thromboxane A2 (TxA2)</topic><topic>Thromboxane A2 - physiology</topic><topic>TRACER TECHNIQUES</topic><topic>Tritium</topic><topic>TRITIUM COMPOUNDS</topic><topic>VASCULAR DISEASES</topic><topic>VASOCONSTRICTION</topic><topic>Vasoconstriction - drug effects</topic><topic>VERTEBRATES</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Eltze, Manfrid</creatorcontrib><creatorcontrib>Sanders, Karl H.</creatorcontrib><creatorcontrib>Boss, Hildegard</creatorcontrib><creatorcontrib>Boer, Rainer</creatorcontrib><creatorcontrib>Ulrich, Wolf-Rüdiger</creatorcontrib><creatorcontrib>Flockerzi, Dieter</creatorcontrib><collection>Istex</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><collection>OSTI.GOV</collection><jtitle>Chirality (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Eltze, Manfrid</au><au>Sanders, Karl H.</au><au>Boss, Hildegard</au><au>Boer, Rainer</au><au>Ulrich, Wolf-Rüdiger</au><au>Flockerzi, Dieter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stereoselective inhibition of thromboxane-induced coronary vasoconstriction by 1,4-dihydropyridine calcium channel antagonists</atitle><jtitle>Chirality (New York, N.Y.)</jtitle><addtitle>Chirality</addtitle><date>1990</date><risdate>1990</risdate><volume>2</volume><issue>4</issue><spage>233</spage><epage>240</epage><pages>233-240</pages><issn>0899-0042</issn><eissn>1520-636X</eissn><abstract>The biological activity of the (+)‐S‐ and (−)‐R‐enantiomers of niguldipine, of the (−)‐S‐ and (+)‐R‐enantiomers of felodipine and nitrendipine, and of rac‐nisoldipine and rac‐nimodipine was investigated in vitro and in vivo. Inhibition of coronary vasoconstriction due to the thromboxane A2 (TxA2)‐mimetic U‐46619 in guinea pig Langendorff hearts, displacement of (+)‐[3H]isradipine from calcium channel binding sites of guinea pig skeletal muscle T‐tubule membranes, and blood pressure reduction in spontaneously hypertensive rats were determined. The enantiomers were obtained by stereoselective synthesis. Cross‐contamination was <0.5% for both S‐ and R‐enantiomers of niguldipine and nitrendipine and <1% for those of felodipine. From the doses necessary for a 50% inhibition of coronary vasoconstriction, stereoselectivity ratios for (+)‐(S)‐/(−)‐(R)‐niguldipine, (−)‐(S)‐/(+)‐(R)‐felodipine, and (−)‐(S)‐/(+)‐(R)‐nitrendipine of 28, 13, and 7, respectively, were calculated. The potency ratio racnisoldipine/rac‐nimodipine was 3.5. Ratios obtained from binding experiments and antihypertensive activity were (+)‐(S)‐/(−)‐(R)‐niguldipine = 45 and 35, (−)‐(S)‐/(+)‐(R)‐felodipine = 12 and 13, (−)‐(S)‐/(+)‐(R)‐nitrendipine = 8 and 8, and rac‐nisoldipine/rac‐nimodipine = 8 and 7, respectively. Highly significant correlations were found between the in vitro potency of the substances to prevent U‐46619‐induced coronary vasoconstriction and their affinity for calcium channel binding sites as well as their antihypertensive activity. The mechanism of TxA2‐induced coronary vasoconstriction in guinea pig Langendorff hearts can be readily explained by a transmembrane influx of extracellular Ca2+ susceptible to stereoselective blockade by 1,4‐dihydropyridine calcium channel antagonists.</abstract><cop>New York</cop><pub>Alan R. Liss, Inc</pub><pmid>1964575</pmid><doi>10.1002/chir.530020408</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0899-0042 |
| ispartof | Chirality (New York, N.Y.), 1990, Vol.2 (4), p.233-240 |
| issn | 0899-0042 1520-636X |
| language | eng |
| recordid | cdi_osti_scitechconnect_5583743 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | 1,4‐dihydropypyridine enantiomers 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid 4-dihydropypyridine enantiomers 550201 - Biochemistry- Tracer Techniques ANIMALS ARTERIES AZINES BASIC BIOLOGICAL SCIENCES Binding, Competitive BIOCHEMICAL REACTION KINETICS BLOOD PRESSURE BLOOD VESSELS BODY calcium channel binding Calcium Channel Blockers - pharmacology Calcium Channels - drug effects Calcium Channels - metabolism CARDIOVASCULAR DISEASES CARDIOVASCULAR SYSTEM CELL CONSTITUENTS Cell Membrane - metabolism CELL MEMBRANES CORONARIES coronary vasoconstriction Dihydropyridines - metabolism Dihydropyridines - pharmacology DISEASES GUINEA PIGS HEART Heart - drug effects Heart - physiology HETEROCYCLIC COMPOUNDS HYDROGEN COMPOUNDS HYPERTENSION IN VITRO In Vitro Techniques IN VIVO INHIBITION ISOTOPE APPLICATIONS Isradipine KINETICS Male MAMMALS MEMBRANE PROTEINS MEMBRANES MUSCLES Muscles - metabolism ORGANIC COMPOUNDS ORGANIC NITROGEN COMPOUNDS ORGANS PORINS Prostaglandin Endoperoxides, Synthetic - pharmacology PROSTAGLANDINS PROTEINS PYRIDINES Pyridines - metabolism Radioligand Assay RATS Rats, Inbred SHR REACTION KINETICS RECEPTORS RODENTS Stereoisomerism stereoselectivity Structure-Activity Relationship STRUCTURE-ACTIVITY RELATIONSHIPS SYMPTOMS thromboxane A2 (TxA2) Thromboxane A2 - physiology TRACER TECHNIQUES Tritium TRITIUM COMPOUNDS VASCULAR DISEASES VASOCONSTRICTION Vasoconstriction - drug effects VERTEBRATES |
| title | Stereoselective inhibition of thromboxane-induced coronary vasoconstriction by 1,4-dihydropyridine calcium channel antagonists |
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