| AT1 angiotensin II receptor inhibition in pacing-induced heart failure: effects on left ventricular performance and regional blood flow patterns. | |
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MedLine Citation:
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PMID: 9924853 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: AT1 angiotensin II (AT1 Ang II) receptor activation has been shown to cause increased vascular resistance in the systemic (SVR), pulmonary (PVR), and coronary vasculature which may be of particular importance in the setting of congestive heart failure (CHF). The overall goal of this study was to examine the effects of acute AT1 Ang II receptor inhibition on left ventricular (LV) pump function, systemic hemodynamics, and regional blood flow patterns in the normal state and with CHF, both at rest and with treadmill-induced exercise. METHODS AND RESULTS: Pigs (25 kg) were instrumented to measure cardiac output (CO), SVR, and PVR, and LV myocardial blood flow distribution in the conscious state and were assigned to one of two groups: (1) pacing-induced CHF (240 bpm for 3 weeks, n = 6) or (2) sham controls (n = 5). Measurements were obtained at rest and after treadmill exercise (15 degrees for 10 minutes). Studies were repeated 30 minutes after intravenous infusion of a low (1.1 mg/kg) or high (125 mg/kg) dose of the AT1 Ang II antagonist, valsartan. The low dose of valsartan reduced the Ang II pressor response by approximately 50% but had a minimal effect on arterial pressure, whereas the high dose eliminated the Ang II pressor response and reduced resting blood pressure by approximately 20%. With CHF, CO was reduced at rest (2.5+/-0.2 v 3.9+/-0.1 L/min) and with exercise (6.4+/-0.5 v 7.8+/-0.5 L/min) compared with controls (P < .05). Valsartan at the low and high dose increased resting CO by 28% in the control and CHF groups, but did not affect CO with exercise. Resting SVR in the CHF group was higher than controls (2,479+/-222 v 1,877+/-65 dyne x s x cm(-5), P < .05), but SVR fell to a similar degree with exercise (1,043+/-98 v 1,000+/-77 dyne x s x cm(-5)). The low and high dose of valsartan reduced resting SVR by more than 30% in both the control and CHF groups. PVR was increased by more than twofold in the CHF group at rest. The high dose of valsartan reduced resting PVR with CHF, but had no further effect with exercise. LV myocardial blood flow was reduced with pacing CHF, particularly with exercise. With exercise and CHF, a low or high dose of valsartan reduced coronary vascular resistance, but LV myocardial blood flow remained reduced from normal values. CONCLUSIONS: Heightened AT1 Ang II receptor activity occurred in this model of CHF, which contributed to alterations in systemic hemodynamics and vascular resistive properties. By using a low dose of a selective AT1 Ang II receptor antagonist reduced SVR, PVR, and coronary vascular resistive properties and therefore may provide beneficial effects in a setting of CHF. |
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Authors:
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M J Clair; R S Krombach; J W Hendrick; W V Houck; L Hebbar; S B Kribbs; G Rios; S Whitebread; R Mukherjee; M de Gasparo; F G Spinale |
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Publication Detail:
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Type: 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: Journal of cardiac failure Volume: 4 ISSN: 1071-9164 ISO Abbreviation: J. Card. Fail. Publication Date: 1998 Dec |
Date Detail:
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Created Date: 1999-03-29 Completed Date: 1999-03-29 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9442138 Medline TA: J Card Fail Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 311-23 Citation Subset: IM |
Affiliation:
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Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston 29425-2279, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin II
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antagonists & inhibitors* Animals Antihypertensive Agents / administration & dosage, pharmacology* Cardiac Pacing, Artificial Coronary Vessels / drug effects, physiology Disease Models, Animal Exercise Test Heart Failure / physiopathology* Hemodynamics Male Receptors, Angiotensin / antagonists & inhibitors* Regional Blood Flow Swine Tetrazoles / administration & dosage, pharmacology* Valine / administration & dosage, analogs & derivatives*, pharmacology Vascular Resistance / drug effects Ventricular Function, Left* |
| Grant Support | |
ID/Acronym/Agency:
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HL-45024/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antihypertensive Agents; 0/Receptors, Angiotensin; 0/Tetrazoles; 11128-99-7/Angiotensin II; 137862-53-4/valsartan; 7004-03-7/Valine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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