| Converting enzyme inhibitors and the role of the sulfhydryl group in the potentiation of exo- and endogenous nitrovasodilators. | |
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MedLine Citation:
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PMID: 1720843 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In this study, the effect of bradykinin on coronary flow in the isolated rat heart was significantly potentiated when cysteine or the sulfhydryl-containing converting enzyme inhibitors captopril and zofenoprilat were administered simultaneously. In contrast, the effect of concomitant administration of enalaprilat only slightly increased the effect of bradykinin on coronary flow. In nitrate-tolerant hearts of rats pretreated with isosorbide dinitrate (15 mg daily), the increase in coronary flow by nitroglycerin and bradykinin was significantly less when compared to control hearts. The effect of captopril was not affected by pretreatment. The involvement of endothelium-derived relaxing factor (EDRF) in the effect of captopril was apparent from experiments with L-arginine, the precursor of EDRF, and L-NMMA, the "false" precursor of EDRF. L-Arginine increased the effect of captopril, whereas L-NMMA showed a competitive antagonism for the effect of captopril on coronary flow in the isolated rat heart. Clinically, the effect of captopril was studied in 10 patients with stable, exercise-induced angina pectoris that had been treated for 3 weeks with slow-release isosorbide dinitrate (20 mg four times daily). At day 7, a baseline exercise test was obtained. Subsequently, patients with chest pain and at least 1-mm ST-segment depression on the ECG during exercise were included. They received on day 14 and 21 either captopril (25 mg) or placebo 1 h before exercise testing in a randomized, double-blind, crossover design. Captopril significantly improved the combined score of maximal ST-segment depression, maximal workload, and time to angina when compared to placebo. No differences in the pressure-rate index at rest and during exercise were seen. These results indicate that the sulfhydryl group of certain angiotensin converting enzyme inhibitors can potentiate their effect on the endogenous nitrovasodilator EDRF. In the clinical situation, this may lead to an improved exercise performance in patients with stable angina pectoris during chronic nitrate treatment, independent of its systemic vascular effects. |
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Authors:
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W H van Gilst; P A de Graeff; M J de Leeuw; E Scholtens; H Wesseling |
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Publication Detail:
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Type: Clinical Trial; In Vitro; Journal Article; Randomized Controlled Trial |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: 18 ISSN: 0160-2446 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 1991 Sep |
Date Detail:
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Created Date: 1992-01-14 Completed Date: 1992-01-14 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: 429-36 Citation Subset: IM |
Affiliation:
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Department of Pharmacology/Clinical Pharmacology, University of Groningen, The Netherlands. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aged Angina Pectoris / drug therapy Angiotensin-Converting Enzyme Inhibitors / pharmacology* Animals Arginine / analogs & derivatives, pharmacology Blood Pressure / drug effects Bradykinin / antagonists & inhibitors, pharmacology Captopril / pharmacology Coronary Circulation / drug effects Cysteine / pharmacology Dose-Response Relationship, Drug Humans Isosorbide Dinitrate / pharmacology Male Middle Aged Nitric Oxide / physiology Nitro Compounds / pharmacology* Rats Rats, Inbred Strains Sulfhydryl Compounds / pharmacology* Vasodilator Agents / pharmacology* omega-N-Methylarginine |
| Chemical | |
Reg. No./Substance:
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0/Angiotensin-Converting Enzyme Inhibitors; 0/Nitro Compounds; 0/Sulfhydryl Compounds; 0/Vasodilator Agents; 10102-43-9/Nitric Oxide; 17035-90-4/omega-N-Methylarginine; 52-90-4/Cysteine; 58-82-2/Bradykinin; 62571-86-2/Captopril; 74-79-3/Arginine; 87-33-2/Isosorbide Dinitrate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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