| Cardiorenal and humoral properties of a novel direct soluble guanylate cyclase stimulator BAY 41-2272 in experimental congestive heart failure. | |
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MedLine Citation:
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PMID: 12578869 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: BAY 41-2272 is a recently introduced novel orally available agent that directly stimulates soluble guanylate cyclase (sGC) and sensitizes it to its physiological stimulator, nitric oxide. To date, its therapeutic actions in congestive heart failure (CHF) remain undefined. We characterized the cardiorenal actions of intravenous BAY 41-2272 in a canine model of CHF and compared it to nitroglycerin (NTG). METHODS AND RESULTS: CHF was induced by rapid ventricular pacing for 10 days. Cardiorenal and humoral function were assessed at baseline and with administration of 2 doses of BAY 41-2272 (2 and 10 micro g x kg(-1) x min(-1); n=8) or NTG (1 and 5 micro g x kg(-1) x min(-1); n=6). Administration of 10 micro g x kg(-1) x min(-1) BAY 41-2272 reduced mean arterial pressure (113+/-8 to 94+/-6 mm Hg; P<0.05), pulmonary artery pressure (29+/-2 to 25+/-2 mm Hg; P<0.05), and pulmonary capillary wedge pressure (25+/-2 to 20+/-2 mm Hg; P<0.05). Cardiac output (2.1+/-0.2 to 2.3+/-0.2 L/min; P<0.05) and renal blood flow (131+/-17 to 162+/-18 mL/min; P<0.05) increased. Glomerular filtration rate was maintained. There were no changes in plasma renin activity, angiotensin II, or aldosterone. NTG mediated similar hemodynamic changes and additionally decreased right atrial pressure and pulmonary vascular resistance. CONCLUSION: The new sGC stimulator BAY 41-2272 potently unloaded the heart, increased cardiac output, and preserved glomerular filtration rate without activation of the renin-angiotensin-aldosterone system in experimental CHF. These beneficial properties make direct sGC stimulation with BAY 41-2272 a promising new strategy for the treatment of cardiovascular diseases such as CHF. |
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Authors:
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Guido Boerrigter; Lisa C Costello-Boerrigter; Alessandro Cataliotti; Toshihiro Tsuruda; Gail J Harty; Harald Lapp; Johannes-Peter Stasch; John C Burnett |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Circulation Volume: 107 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2003 Feb |
Date Detail:
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Created Date: 2003-02-11 Completed Date: 2003-02-26 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
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Languages: eng Pagination: 686-9 Citation Subset: AIM; IM |
Affiliation:
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Cardiorenal Research Laboratory, Mayo Clinic and Foundation, Rochester, MN 55905, USA. boerrigter.guido@mayo.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aldosterone
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blood Angiotensin II / blood Animals Cardiac Output / drug effects Cardiac Pacing, Artificial Disease Models, Animal Dogs Drug Evaluation, Preclinical Glomerular Filtration Rate / drug effects Guanylate Cyclase Heart / drug effects* Heart Failure / drug therapy* Heart Function Tests / drug effects Hemodynamics / drug effects Injections, Intravenous Kidney / drug effects* Kidney Function Tests Male Nitroglycerin / pharmacology Pyrazoles / pharmacology*, therapeutic use Pyridines / pharmacology*, therapeutic use Receptors, Cytoplasmic and Nuclear / drug effects, metabolism* Renin / blood Renin-Angiotensin System / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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HL-36634/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine; 0/Pyrazoles; 0/Pyridines; 0/Receptors, Cytoplasmic and Nuclear; 11128-99-7/Angiotensin II; 52-39-1/Aldosterone; 55-63-0/Nitroglycerin; EC 3.4.23.15/Renin; EC 4.6.1.2/Guanylate Cyclase; EC 4.6.1.2/soluble guanylyl cyclase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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