L-carnitine attenuates cardiac impairment but not vascular dysfunction in DOCA-salt hypertensive rats

O'Brien, Daniel and Chunduri, Prasad and Iyer, Abishek and Brown, Lindsay (2010) L-carnitine attenuates cardiac impairment but not vascular dysfunction in DOCA-salt hypertensive rats. Basic and Clinical Pharmacology and Toxicology, 106 (4). pp. 296-301. ISSN 1742-7835

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Abstract

L-Carnitine is an important co-factor in fatty acid metabolism by mitochondria. This study has determined whether oral administration of L-carnitine prevents remodelling and the development of impaired cardiovascular function in deoxycorticosterone acetate (DOCA)-salt hypertensive rats (n = 6–12; #p < 0.05 versus DOCA-salt). Uninephrectomized rats administered DOCA (25 mg every 4th day s.c.) and 1% NaCl in drinking water for 28 days developed cardiovascular remodelling shown as systolic hypertension, left ventricular hypertrophy, increased thoracic aortic and left ventricular wall thickness, increased left ventricular inflammatory cell infiltration together with increased interstitial collagen and increased passive diastolic stiffness and vascular dysfunction with increased plasma malondialdehyde concentrations. Treatment with L-carnitine (1.2% in food; 0.9 mg⁄g⁄day in DOCA-salt rats) decreased blood pressure (DOCA-salt 169 € 2; + L-carnitine 148 € 6# mmHg), decreased left ventricular wet weights (DOCA-salt 3.02 € 0.07; + L-carnitine 2.72 € 0.06# mg⁄ g body-wt), decreased inflammatory cells in the replacement fibrotic areas, reduced left ventricular interstitial collagen content (DOCA-salt 14.4 € 0.2; + L-carnitine 8.7 € 0.5# % area), reduced diastolic stiffness constant (DOCA-salt 26.9 € 0.5; + L-carnitine 23.8 € 0.5# dimensionless) and decreased plasma malondialdehyde concentrations (DOCA-salt 26.9 € 0.8; + L-carnitine 21.2 € 0.4# lmol ⁄ l) without preventing endothelial dysfunction. L-carnitine attenuated the cardiac remodelling and improved cardiac function in DOCA-salt hypertension but produced minimal changes in aortic wall thickness and vascular function. This study suggests that the mitochondrial respiratory chain is a significant source of reactive oxygen species in the heart but less so in the vasculature in DOCA-salt rats, underlying the relatively selective cardiac responses to L-carnitine treatment.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Authors retain copyright.
Depositing User: Professor Lindsay Brown
Faculty / Department / School: Historic - Faculty of Sciences - Department of Biological and Physical Sciences
Date Deposited: 03 Jan 2011 09:27
Last Modified: 02 Jul 2013 23:50
Uncontrolled Keywords: animal cell; animal experiment; animal model; animal tissue; antiinflammatory activity; arterial wall thickness; article; attenuation; blood pressure regulation; blood vessel reactivity; cardiovascular function; cell infiltration; controlled study; diastole; disease course; endothelial dysfunction; heart disease; heart function; heart left ventricle hypertrophy; heart left ventricle mass; heart mitochondrion; heart muscle fibrosis; heart muscle perfusion; heart ventricle hypertrophy; heart ventricle remodeling; inflammatory cell; isolated heart; lipid peroxidation; male; nonhuman; priority journal; rat; respiratory chain; systolic blood pressure; systolic hypertension; thoracic aorta; uninephrectomy; vascular disease; vascular ring
Fields of Research (FOR2008): 11 Medical and Health Sciences > 1104 Complementary and Alternative Medicine > 110499 Complementary and Alternative Medicine not elsewhere classified
11 Medical and Health Sciences > 1115 Pharmacology and Pharmaceutical Sciences > 111501 Basic Pharmacology
11 Medical and Health Sciences > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl. Cardiovascular Diseases)
Socio-Economic Objective (SEO2008): C Society > 92 Health > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases
Identification Number or DOI: doi: 10.1111/j.1742-7843.2009.00480.x
URI: http://eprints.usq.edu.au/id/eprint/7743

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