| Effects of sumatriptan on coronary flow and left ventricular function in the isolated perfused guinea pig heart. | |
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MedLine Citation:
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PMID: 9733357 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The effects of the 5-HT1B/D receptor agonist, sumatriptan, on coronary flow (CF) and left ventricular function in the isolated perfused guinea pig heart were investigated in the presence and absence of coronary endothelial dysfunction induced by nitric oxide (NO) synthase inhibition with Nomega-nitro-L-arginine methyl ester (L-NAME; 10 microM). Hearts were perfused under constant pressure (80 cm H2O) with oxygenated (95% O2/5% CO2) Krebs bicarbonate buffer (pH 7.4) and were driven at 4 Hz. In the absence of L-NAME (n=37), sumatriptan (0.1-32 microM) failed statistically significantly to affect left ventricular developed pressure (LVDP; maximal change, -8.1+/-1.8%; NS vs. vehicle), left ventricular end-diastolic pressure (LVEDP; +10.4+/-9.8%, NS), or CF (-12.2+/-1.4%; NS compared with vehicle). L-NAME per se significantly reduced coronary flow (CF; -26.3+/-2.9%; p < 0.001), thereby increasing coronary vascular tone, and decreased LVDP (-17.1+/-1.8%; p < 0.01). In hearts perfused with L-NAME (10 microM; n=61), sumatriptan (0.1-32 microM) still failed significantly to affect CF (maximal change, 0.2+/-5.7%, NS) but concentration-dependently increased LVEDP [maximal increase, 89.0+/-30.3%; p < 0.05; geometric mean EC50 3.6 (2.9-5.7) microM], which was not prevented by the 5-HT1B/D receptor antagonist, GR 127935 (0.1 microM; maximal increase, 51.8+/-11.1%; n=48, NS compared with sumatriptan alone). In conclusion, sumatriptan failed significantly to affect CF even in the presence of endothelial dysfunction. LV function similarly remained unaffected in normal hearts, but sumatriptan produced diastolic contracture in the presence of coronary endothelial dysfunction by a mechanism apparently not involving 5-HT1B/D receptors. Collectively the data indicate that 5-HT1B/D receptor expression or effector coupling or both are absent or low in the guinea pig heart, because no detectable functional responses were observed. |
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Authors:
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B Le Grand; B Vié; G W John |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: 32 ISSN: 0160-2446 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 1998 Sep |
Date Detail:
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Created Date: 1998-11-23 Completed Date: 1998-11-23 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7902492 Medline TA: J Cardiovasc Pharmacol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 435-42 Citation Subset: IM |
Affiliation:
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Centre de Recherche Pierre Fabre, Division of Cardiovascular Diseases, Castres, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Coronary Circulation / drug effects* Diastole / drug effects Dihydroergotamine / pharmacology Endothelium, Vascular / physiology Guinea Pigs NG-Nitroarginine Methyl Ester / pharmacology Oxadiazoles / pharmacology Oxazoles / pharmacology Oxazolidinones* Perfusion Piperazines / pharmacology Rabbits Receptor, Serotonin, 5-HT1B Receptor, Serotonin, 5-HT1D Receptors, Serotonin / drug effects, physiology Serotonin Agonists / pharmacology* Sumatriptan / pharmacology* Tryptamines Ventricular Function, Left / drug effects* |
| Chemical | |
Reg. No./Substance:
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0/Oxadiazoles; 0/Oxazoles; 0/Oxazolidinones; 0/Piperazines; 0/Receptor, Serotonin, 5-HT1B; 0/Receptor, Serotonin, 5-HT1D; 0/Receptors, Serotonin; 0/Serotonin Agonists; 0/Tryptamines; 103628-46-2/Sumatriptan; 139264-17-8/zolmitriptan; 148672-13-3/GR 127935; 50903-99-6/NG-Nitroarginine Methyl Ester; 511-12-6/Dihydroergotamine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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