| Potentiation of sildenafil-induced hypotension is minimal with nitrates generating a radical intermediate. | |
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MedLine Citation:
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PMID: 11444498 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Recently the new specific phosphodiesterase-5 inhibitor sildenafil was introduced into therapy for erectile dysfunction. Because of the phosphodiesterase-5 inhibitor-induced increases of cyclic GMP in the vasculature, vasodilation in various vascular beds is induced, which in combination with various nitrovasodilators (e.g., when used simultaneously for the treatment of coronary artery disease), may lead to excessive hypotension. Thus nitrovasodilators are contraindicated when sildenafil may be used and reports of a number of accidents have recently been published. We therefore studied the acute interactions of glyceryl trinitrate (GTN), pentaerythritol tetranitrate (PETN), and isosorbide dinitrate (ISDN) with sildenafil in six chronically instrumented conscious dogs for each nitrate to assess the magnitude of blood pressure drops (and compensatory increases in heart rate) during a 24-h nitrate administration (infusion into the pulmonary artery). Sildenafil (3 mg/kg) was given orally (after a 24-h fast) 30 min after start of nitrate infusion. GTN, PETN, or ISDN (which follow different steps of metabolic conversion to nitric oxide) were applied at submaximal dosages leading to 90% of maximal coronary artery dilation at 1.5 microg/kg per min, 0.75 microg/kg per min, or 6 microg/kg per min, respectively. During GTN infusion sildenafil caused a maximum drop in mean blood pressure of 21 +/- 3 mm Hg (rise in heart rate from 117.0 +/- 7.2 to 126.0 +/- 6 .0/min) and during ISDN infusion of 18 +/- 3 mm Hg (rise in heart rate from 115.0 +/- 7.0 to 125 +/- 6/min), which was significantly less (p < 0.01) during PETN (only 6 +/- 1 mm Hg with a rise in heart rate from 107.0 +/- 5.0 to 122.0 +/- 7.0/min). When sildenafil is used during exposure to nitrates (e.g., in coronary artery disease), the PETN-induced drop in blood pressure at equi-effective dosages (with regard to coronary dilation) is substantially smaller compared with that of GTN or ISDN, which is probably because of lesser potentiation of phosphodiesterase-5 inhibitor-induced effects in the arteriolar bed, thus minimizing critical drops in blood pressure. |
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Authors:
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M Schwemmer; E Bassenge; M Stoeter; B Hartmann; U Hess; B Fink |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: 38 ISSN: 0160-2446 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 2001 Jul |
Date Detail:
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Created Date: 2001-07-10 Completed Date: 2001-12-04 Revised Date: 2007-11-15 |
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: 149-55 Citation Subset: IM |
Affiliation:
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Albert-Ludwigs-University, Institute for Applied Physiology, Freiburg, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Pressure / drug effects, physiology Dogs Dose-Response Relationship, Drug Drug Synergism Female Free Radicals / metabolism Heart Rate / drug effects, physiology Hypotension / chemically induced* Male Nitrates / metabolism*, pharmacology* Phosphodiesterase Inhibitors / pharmacology* Piperazines / pharmacology* Purines Sulfones |
| Chemical | |
Reg. No./Substance:
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0/Free Radicals; 0/Nitrates; 0/Phosphodiesterase Inhibitors; 0/Piperazines; 0/Purines; 0/Sulfones; 139755-83-2/sildenafil |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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