| Effects of fixed-dose isosorbide dinitrate/hydralazine on diastolic function and exercise capacity in hypertension-induced diastolic heart failure. | |
| | |
MedLine Citation:
|
PMID: 19620510 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Hypertension-induced diastolic heart failure accounts for a large proportion of all heart failure presentations. Hypertension also induces left ventricular (LV) hypertrophy. Fixed-dose isosorbide dinitrate/hydralazine (HISDN) decreased mortality in human systolic heart failure but it is unknown whether it improves maladaptive myocardial remodeling. We sought to test the hypothesis that chronic HISDN modulates LV hypertrophy and myocardial remodeling in hypertension-induced diastolic heart failure. FVB mice underwent either saline (n=18) or aldosterone (n=28) infusion. All underwent uninephrectomy and drank 1% salt water for 4 weeks. Mice were randomized after surgery to regular chow or chow containing HISDN (isosorbide dinitrate: 26 mg/kg per day; hydralazine: 50 mg/kg per day) for 4 weeks. Aldosterone infusion increased tail-cuff blood pressure (161+/-3 mm Hg) versus saline-infused mice (129+/-2 mm Hg). Aldosterone induced LV hypertrophy versus saline-infused mice (LV:body weight ratio: 4.2+/-0.1 versus 3.6+/-0.1 mg/g). HISDN attenuated the aldosterone-induced increased in systolic blood pressure (137+/-5 mm Hg) and also lowered blood pressure in saline-infused mice (114+/-2 mm Hg). However, HISDN did not cause LV hypertrophy regression in aldosterone-infused mice. Aldosterone increased LV end-diastolic dimensions that were not attenuated by HISDN. Similarly, neither aldosterone infusion nor HISDN affected LV end-systolic dimensions. LV ejection fraction and wet:dry lung ratio were not different between aldosterone-untreated and aldosterone-HISDN mice. However, mitral Doppler E/A ratio (a measure of diastolic function), exercise capacity, and plasma soluble vascular cell adhesion molecule 1 levels were improved in aldosterone-HISDN hearts. In conclusion, fixed-dose HISDN improved hypertension, diastolic function, and exercise capacity and reduced soluble vascular cell adhesion molecule 1 levels. There were no reductions in LV hypertrophy, cardiac fibrosis, or pulmonary congestion. These functional improvements are likely related to extracardiac effects, such as effects on the vasculature. |
| | |
Authors:
|
Richard M Wilson; Deepa S De Silva; Kaori Sato; Yasuhiro Izumiya; Flora Sam |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-07-20 |
Journal Detail:
|
Title: Hypertension Volume: 54 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2009 Sep |
Date Detail:
|
Created Date: 2009-08-20 Completed Date: 2009-09-18 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
|
Languages: eng Pagination: 583-90 Citation Subset: IM |
Affiliation:
|
Whitaker Cardiovascular Institute, Boston University School of Medicine, Evans Department of Medicine and Cardiovascular Section, 715 Albany Street, Boston, MA 02118, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Aldosterone
/
administration & dosage,
toxicity Animals Atrial Natriuretic Factor / genetics Blood Pressure / drug effects* Cytokines / genetics Diastole Drug Therapy, Combination Echocardiography, Doppler Exercise Test Fibrosis Gene Expression / drug effects Heart / drug effects, physiopathology Heart Failure / drug therapy*, etiology, physiopathology Hydralazine / pharmacology*, therapeutic use Hypertension / drug therapy*, etiology, physiopathology Isosorbide Dinitrate / pharmacology*, therapeutic use Male Mice Myocardium / pathology Reverse Transcriptase Polymerase Chain Reaction Sarcoplasmic Reticulum Calcium-Transporting ATPases / genetics Sodium Chloride, Dietary / administration & dosage, toxicity Vascular Cell Adhesion Molecule-1 / blood Vasodilator Agents / pharmacology, therapeutic use |
| Grant Support | |
ID/Acronym/Agency:
|
HL 079099/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Cytokines; 0/Sodium Chloride, Dietary; 0/Vascular Cell Adhesion Molecule-1; 0/Vasodilator Agents; 52-39-1/Aldosterone; 85637-73-6/Atrial Natriuretic Factor; 86-54-4/Hydralazine; 87-33-2/Isosorbide Dinitrate; EC 3.6.3.8/Atp2a2 protein, mouse; EC 3.6.3.8/Sarcoplasmic Reticulum Calcium-Transporting ATPases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Regional release and clearance of C-type natriuretic peptides in the human circulation and relation ...
Next Document: Role of mineralocorticoid receptor on experimental cerebral aneurysms in rats.